Midterm 2 Flashcards
1
Q
Cells producing steroid hormones tend to have extensive networks of ______ ER
A
Smooth
2
Q
Cells involved in synthesis of secretory proteins have prominent _____ ER networks
A
Rough
3
Q
Where is the tER, transitional Endoplasmic Reticulum, located?
A
At the edge of rough ER
4
Q
What is the function of the tER, transitional Endoplasmic Reticulum?
A
The formation of vesicles that shuttle lipids and proteins from the ER to the Golgi: Assembling and budding vesicles for transport to other compartments or secretion (Sec12, Sar1, COPII proteins)
5
Q
What does the smooth Endoplasmic Reticulum form?
A
Tubular structures
6
Q
What does the rough Endoplasmic Reticulum form?
A
Large, flattened sacs
7
Q
What is special about the sER?
A
It has no ribosomes
8
Q
What is the function of the sER?
A
- Membrane, Steroid and Lipid biosynthesis
- Drug detoxification
- Carbohydrate metabolism
- Calcium Storage
9
Q
What is the function of the rER?
A
It is the place where proteins are inserted into the ER
- Co-translational protein import
- Folding of secreted and membrane proteins
- Addition of carbohydrates to glycoproteins
- Recognition and removal of misfolded proteins
- Assembly and budding of vesicles for transport to other compartments or secretion
F A I R R A B
10
Q
What is a special quality of the rER?
A
Sec61 translocon complexes with ribosomes on the cytosolic membrane side
11
Q
What is vesicular transport?
A
The process of delivering components (proteins and lipids) to other compartments for formation of organelles and cell function
12
Q
Anterograde transport is from ____ to the ______
A
From the ER to the PM
13
Q
Retrograde transport is from ____ to the ____
A
From the PM to the ER
14
Q
Why is vesicular transport so important?
A
It is critical for the balance and flow of lipids and membrane proteins
15
Q
What is the Endoplasmic Reticulum?
A
It is a continuous network of flattened sacs, tubules and vesicles through a cell’s cytoplasm
16
Q
What is the space inside the ER?
A
The ER lumen
17
Q
What are the membrane-bound sacs inside the ER called?
A
Cisternae
18
Q
What is the Endomembrane system?
A
A set of membranes that form a single functional and developmental unit
19
Q
What does the Endomembrane system consist of?
A
The nuclear membrane, ER, Golgi, lysosomes, vesicles, endosomes, and the plasma membrane
20
Q
How is the Endomembrane system connected?
A
Directly or indirectly through vesicular transport
21
Q
Explain sER drug detoxification
A
Hydroxylation: adding hydroxyl groups to a drug in order to increase solubility and make it easier to excrete them from the body
Enzymes involved in the drug detoxification process can be upregulated and sER can proliferate due to drug exposure
22
Q
Explain sER Carbohydrate metabolism
A
Breaking down stored glycogen using glucose-6-phosphatase, which is an enzyme unique to the sER. This enzyme hydrolyzes the phosphate from glucose-6-phosphate to form free glucose
23
Q
Explain sER Calcium Storage
A
Calcium ions are actively pumped from the cytoplasm into the ER for storage, and calcium pumps and channels are enriched in smooth ER
24
Q
Explain sER Steroid Biosynthesis
A
Enzymes responsible for steroid biosynthesis are present at the sER
24
What is the Golgi complex?
A series of flattened membrane-bound cisternae, and is functionally and physically linked to the ER
25
What is the function of the Golgi Complex?
It has a central role in membrane and protein trafficking in eukaryotic cells, where glycoproteins and membrane lipids from the ER undergo further processing and are sorted and packaged for transport
26
What is a series of cisternae called?
A Golgi stack
27
Secretory cells have how many Golgi stacks?
Hundreds or thousands
28
What are the two faces of the Golgi stack?
The CGN, Cis Golgi Network
The TGN, Trans Golgi Network
29
Describe the CGN
The cis face is oriented towards the ER, therefore the Golgi compartment on this side is called the CGN
30
Describe the TGN
The trans face is oriented away from the ER, therefore the Golgi compartment on this side is called the TGN
31
Proteins and lipids are delivered from the ___ to the ER
CGN
32
Proteins and lipids leave the Golgi in transport vesicles that continuously bud from the ___ destined for the cell surface or other organelles
TGN
33
What is between the TGN and CGN?
Medial cisternae, where much of the processing of proteins occurs
34
Each compartment shows _____ _______, containing specific proteins unique to each portion of the network
Biochemical polarity
35
Describe N-linked glycosylation
It involves the addition of an oligosaccharide to the nitrogen atom of certain asparagine residues
36
Describe O-linked glycosylation
It involves the addition of an oligosaccharide to the oxygen atom on the hydroxyl group of certain serine or threonine residues
37
What is glycosylation?
The addition of carbohydrate side chains to proteins, which is a big part of protein processing in the ER and Golgi
38
Where do the initial steps of N-glycosylation take place?
The ER
39
Glycosylation can occur co-translationally to promote...
Proper protein folding
40
All added chains in glycosylation initially have a common core oligosaccharide consisting of...
Two units of N-acetylglucosamine
Nine mannose units
Three glucose units
41
What do Calnexin (CNX) and Calreticulin (CRT) do?
They bind to monoglycosylated proteins and promote disulfide bond formation
42
Glucosidase I and II...
Remove 2 glucose residues
43
CNX and CRT are chaperones in that they...
Attempt to aid folding
44
The third glucose is removed by ________ after release from CNX and CRT
Glucosidase II
45
If protein folding is incorrect, a _________ binds to improperly folded proteins and adds back a ________, making the protein a substrate for CNX/CRT binding
Glucosyl transferase (UGGT)
Single glucose unit
46
The competition between UGGT and ER mannosidase I ultimately ______________
Determines the fate of the protein
47
What two enzymes compete to correct protein folding
UGGT and ER mannosidase I
48
ER mannosidase I can bind to remove a mannose residue which triggers _____
READ
49
Where does further processing of N-glycosylated proteins occur?
In the Golgi complex as the glycoproteins move from the CGN to the TGN
50
Terminal N- and O- linked glycosylations are...
Variable and create great diversity
51
The ER and Golgi contain hundreds of different glycosyl transferases?
True
52
What happens after budding from the TGN
Some vesicles move directly to the cell surface and immediately fuse with the PM
53
Constitutive Secretion is an ________ process, ______ and _______ of external signals
Unregulated
Continuous
Independent
54
What is an example of Constitutive secretion
Mucus secretion by the intestinal lining
55
What is Regulated Secretion?
When secretory vesicles accumulate in the cell and only fuse with the PM in response to specific signals
56
What is an example of Regulation secretion?
Neurotransmitter release where secretory vesicles carrying neurotransmitters move close to the site of secretion and remain there until receiving a signal
57
What is the role of depolarization in regulated secretion?
It is the signal that triggers vesicles to release their content by fusion with the PM
58
What is protein trafficking?
Proteins synthesized in the cell must be directed to a variety of locations. Once a protein reaches its destination, it must be prevented from leaving, and so proteins often contain a specific tag which targets it to a transport vesicle that will take it to the correct location
59
What is a protein targeting tag?
An amino acid sequence, hydrophobic domain, or oligosaccharide side chain which is used to target it to a transport vesicle, or to exclude material from certain vesicles
60
How do we maintain ER identity?
By preventing some proteins from escaping the ER and/or by retrieving others from the Golgi
61
What are some retention/retrieval tags that keep proteins in the ER?
RXR (Arg-X-Arg)
Dibasic (KK/disyline on the C-terminus)
RR/Diarginine
KDEL (mammals)
HDEL (yeast)
62
What happens when a protein with a retention tag binds a receptor in the Golgi?
The receptor-cargo complex is packaged into a transport vesicle for return to the ER
63
What is a Golgi-specific protein?
An integral membrane protein with one or more hydrophobic membrane-spanning domains
64
What does the length of the hydrophobic domain determine?
Into which cisternae each protein is incorporated
65
What is exocytosis?
The process by which secretory vesicles release their contents outside the cell. Proteins in a vesicle are released to the exterior of the cell as the vesicle fuses with the PM
66
What is endocytosis?
The process by which cells internalize external materials
67
What are some examples of exocytosis in animals?
Hormones, mucus, milk proteins, digestive enzymes
68
What are some examples of exocytosis in plants?
Enzyme and structural proteins for the cell wall
69
When a vesicle fuses with the PM in exocytosis, the luminal membrane of the vesicle becomes part of....
The outer surface of the PM
70
Glycolipids and glycoproteins that were formed in the ER and Golgi lumen will face the....
Extracellular space
71
What is Polarized secretion?
When exocytosis of specific proteins is limited to a specific surface of the cell
72
What is an example of polarized secretion?
Intestinal cells that secrete digestive enzymes only on the side of the cell that faces into the intestine
73
Why is membrane flow important?
To maintain a steady-state composition of the PM, which is defined by the balance between endocytosis and exocytosis
74
How do endocytosis and exocytosis influence membrane flow?
Endocytosis removes lipids and proteins from the PM, whereas Exocytosis adds lipids and proteins to the PM
75
What is phagocytosis?
The ingestion of large particles up to and including whole cells or organisms. The way unicellular organisms acquire food.
76
Explain phagocytosis in humans
Neutrophils and macrophages use phagocytosis as a means of defence, where they engulf and digest foreign materials or invasive microorganisms found in the bloodstream or injured tissues
77
What are the 4 steps in protein coating?
1. Cargo sorting/Selection/Concentration
2. Coat assembly/Membrane deformation
3. Vesicle budding
4. Vesicle uncoating
78
Why are protein and lipid vesicles called coated vesicles?
Because of the layers of proteins coating their cytosolic surfaces
79
What are some examples of coat protein systems?
Clathrin, COPI, COPII, Caveolin
80
What is the role of coat proteins?
They induce membrane curvature needed for the formation of the vesicles and participate in the collection of specific cargo molecules
81
What are Clathrin-coated vesicles?
Vesicles surrounded by coats make of two multimeric proteins: clathrin and adaptor protein (AP)
82
What does the shape of a clathrin protein and the way it's assembled provide?
The driving force to form a spherical vesicle
83
What is the basic unit of a clathrin lattice?
A triskelion
84
Explain the structure of a triskelion
A multimeric protein composed of 3 heavy chains and 3 light chains which radiate from a central vertex, with the light chains associated with the inner half of each "leg". Triskelions assemble into hexagons and pentagons of the lattice clathrin-coated pits and vesicles
85
All cargo must interact with the vesicle coat?
True, either directly or indirectly
86
Where do coats in the cytoplasm bind?
They bind to specific motifs contained in the cytoplsmic domain of transmembrane proteins
87
Why are many cargo proteins soluble?
They must be able to bind to receptors/adaptors which are transmembrane proteins in order to be collected into a vesicle
88
What are some examples of motifs for protein coat formation?
- Dileucine (AP/clathrin)
- YXX (Tyrosine - anything - anything)
- Dilysin (COPI)
- Diacidic (COPII)
89
What is required for constricting and closing a Clathrin-coated vesicle?
Dynamin
90
What is dynamin?
It is a cytosolic GTPase; as GTPase is hydrolyzed, dynamin rings tighten and separate the vesicle from the PM, which allows clathrin to dissociate once the vesicle has formed and budded
91
How is COPI and COPII vesicle coat assembly initiated?
By members of the Ras superfamily of small GTPases
92
What are the On and Off states of GTPase?
GTP = membrane-bound (on)
GDP = soluble/cytoplasm (off)
93
How is GTPase activated?
Guanine nucleotide exchange factor
94
What does NSF mean?
N-ethylmaleimide sensitive factor
95
What does SNAP mean?
Small NSF attachment protein
96
What does SNARE mean?
SNAP receptor
97
Where are v-SNAREs found?
On vesicles
98
Where are t-SNAREs found?
On target membranes
99
V- and T-SNAREs are complementary molecules that...
Allow recognition between vesicles and their targets
100
What is the role of COPI-coated vesicles?
Retrograde transport from the Golgi back to the ER
101
What are COPI-coated vesicles coated with?
COPI, ARF (ADP ribosylation factor), and a small GTP-binding protein
102
What factor mediates the assembly of a coat?
ARF
103
What is the COPI-coated vesicle cycle?
1. In the cytoplasm, ARF exists in complex with GDP
2. Upon meeding a GEF (Guanine exchange factor) associated with the membrane, the GDP is exchanged for GTP
3. The resulting conformational change in ARF attaches it to the membrane and leads to cargo and COPI association with ARF
4. Assembly of the coat drives vesicle formation
5. Once the vesicle is formed, a GAP (GTPase activating protein) in the donor membrane triggers hydrolysis of GTP to GDP, a conformational change in ARF and release of the coat
104
What is the role of COPII-coated vesicles?
Transport from the ER to the Golgi
105
In yeast, what is the COPII coat assembled from?
Sec13/31 and Sec23/24, and a small GTP-binding protein called SarI
106
What is SarI?
It has an amphipathic helix at the N-terminus, and is similar to ARF. Its process of coat formation is similar to COPI-coated vesicles
107
What is the SNARE hypothesis?
That sorting and targeting of vesicles involves two families of SNARE proteins... once vesicles are formed, additional proteins ensure delivery to the correct destination
108
What is the role of Rab GTPases?
They lock SNARE proteins together in order to facilitate membrane fusion
109
What are tethering proteins?
Tethering proteins act over long distances and attach vesicles to their targets before the SNAREs interact
110
What is Complexin?
A tethering protein that regulates neurotransmitter vesicle fusion, where is clamps SNARE proteins to prevent zippering/fusion (superprimed)
111
When do superprimed vesicles fuse?
When calcium enters the cell
112
Why is Receptor-mediated Endocytosis important?
Cells acquire some substances through this process, and other cells use receptors on the outer cell surface to internalize many macromolecules
113
How does Receptor-mediated Endocytosis regulate cell signalling?
1. Receptors on the cell surface can be stimulated by molecules in the environment, leading to growth, cell division, motility, etc
2. After receiving these signals, cells can internalize the receptors to become less responsive to the stimulus (Desensitization)
3. After internalization of a receptor, the vesicle can fuse with other vesicles that are budding from the TGN to form early endosomes
114
What is Defective Desensitization?
Failure to internalize the receptor which can lead to overstimulation (excess cell division and tumour formation)
115
What is the role of early endosomes?
Sites for sorting and recycling of materials brought into the cell
116
How can we recycle plasma membrane receptors?
Receptors from the Golgi membrane can be recycled through fusion with other vesicles
Acidification of the early endosome can occur facilitated by an ATP-dependent proton pump
The lower pH promotes the removal of the ligand from a receptor to allow recycling back to the Golgi
117
What is a lysosome?
An organelle of the endomembrane system that contains digestive enzymes that are capable of degrading all the major classes of biological macromolecules. They maintain an acidic environment (pH 4.0-5.0) due to their ATP-dependent proton pumps
118
What are the enzymes inside the lysosomes called?
Acid hydrolases
119
How do lysosomes develop?
Lysosomal enzymes are co-translationally synthesized into the ER and trafficked through the secretory pathway to the TGN and then sent to endosomes in transport vesicles. Overtime, endosomes mature into late endosomes, with all the enzymes present, but not engaged in digestion. As the internal environment becomes more acidic, the acid hydrolases become activated through the pumping of protons or through fusion with an existing lysosome.
120
What are lysosomal storage diseases?
They are characterized by the accumulation of substances that cannot be broken down as needed, and most have no treatment
121
What is Autophagy?
When cellular structures that are damaged and are no longer needed can be broken down, and these damaged organelles can be wrapped in a double membrane derived from the ER, forming an autophagosome.
122
What is recycled in Autophagy?
Nucleotides, sugars, amino acids, etc
123
What can trigger Autophagy?
Starvation
124
How does Signal Transduction work?
Cell membranes can regulate the flow of ions between the interior and exterior of the cell. Nerve cells have special mechanisms for using electrical potentials to transmit information over long distances.
Cells can also communicate by sending and receiving regulatory chemical messengers. Receptors are located on receiving cells that can be quite distant from the secreting cell
125
What is Membrane potential?
A fundamental property of all cells, where cells at rest normally have an excess positive charge on the outside and a negative charge on the inside. The resulting electrical potential of the cell is called the resting membrane potential, which is -70mV
126
What is Electrical Excitability?
The unique feature of electrically excitable cells is their response to depolarization, where excitable cells respond with an action potential.
127
How to excitable cells respond to depolarization?
They respond with an action potential, where they have voltage-gated channels in their plasma membranes, and the coordinated opening and closing of the ion channel leads to an action potential
128
Sodium influx leads to a ______ charge inside the cell
Positive
129
How is resting potential established?
By the 3 Sodiums out/2 Potassiums in exchange
130
How is an action potential propagated?
A stimulus triggers the voltage-gated sodium channel and sodium flows into the cell with the gradient. The increase in sodium triggers the opening of potassium channels and they flow out with the gradient. The sodium/potassium exchanger then re-establishes the resting potential
131
What is an electrical synapse?
When a presynaptic neuron is connected to a post synaptic neuron via gap junctions, and the iosn move through the junctions between the cells with no delay in transmission
132
What is a chemical synapse?
When presynaptic and postsynaptic neurons are not connected by gap junctions, but instead a synaptic cleft. A signal at the terminus of the presynaptic neuron must be sent to the postsynaptic neuron chemically
133
What is spatial summation?
Action potentials that are received at a single synapse are usually not sufficient to induce an action potential, and so when many action potentials can neurotransmitter release simultaneously, it is more likely that an action potential with be induced.
134
Postsynaptic neurons can receive both inhibitory and excitatory signals?
True
135
Neurons can receive thousands of inputs from other neurons and physically sum the signals?
True
136
What is chemical messaging?
The second major means of intercellular communication: Cells produce signals by displaying molecules on their surface, or by releasing a chemical signal.
137
What are the different kinds of chemical signals?
Paracrine
Exocrine
Juxtacrine
Autocrine
138
Paracrine signals...
Are diffusible and act over a short range
139
Endocrine signals...
Are produced far from the target tissues, which they reach via the circulatory system
140
Juxtacrine signals...
Require physical contact between sending and receiving cells
141
Autocrine signals...
Act on the same cell that produces them
142
What is a ligand?
A chemical messenger that binds to a target receptor
143
When a messenger reaches its target, it binds to a...
Receptor
144
The ligand is a _____ messenger
Primary
145
How do messengers bind to receptors in a highly specific way?
Through several noncovalent bonds, which is achieved by the binding site on the receptor fitting the messenger very closely with necessary amino acid side chains, positioned to form chemical bonds with the messenger
146
What is a cognate receptor?
A receptor specific for a certain ligand
147
When a receptor is bound to its ligand, it is said to be...
Occupied
148
When a ligand binds to its receptor, it often...
1. Induces a change in receptor conformation
2. Causes receptors to cluster
These both lead to activation
149
What is a second messenger?
Small molecules or ions that relay the signal within a cell, due to ligand binding that triggers production of molecules
150
What are some examples of second messengers?
- cAMP
- Ions
- Gases
- Membrane lipid derivatives
151
What is signal amplification?
The multiplication of the effect of a signal
152
What is signal integration?
Where cells integrate a multitude of signals in order to produce appropriate responses, as a single receptor can activate multiple pathways, or these pathways can converge into the same molecule
153
What is signalling crosstalk?
Where activated components from one pathway affect components of another pathway
154
What are the categories of receptors?
1. Ligand-gated channels
2. Plasma membrane receptors
3. G-proteins
4. Receptor-linked kinases
155
What is the G-protein-coupled receptor?
Ligand-binding causes a change in receptor conformation that activates a particular G-protein. All G-protein-coupled receptors have a similar structure with seven transmembrane helices connected by alternating cytosolic or extracellular loops, and the extracellular portion of each receptor has a unique messenger-binding site
156
How do G-proteins act?
Like molecular switches whose on and off states depends on whether they are bound to GTP or GDP
157
Heterotrimeric G-proteins mediate signal transduction through...
G-protein-linked receptors and have G,G,G subunits
158
How are G-proteins regulated?
The rate of hydrolysis... GTP hydrolysis is greatly enhanced by regulators of G-protein-signalling proteins (RGS)
159
What is cyclic AMP?
cAMP is the second messenger of G-protein signaling formed from cytosolic AMP by adenylyl cyclase, an enzyme that is anchored in the plasma membrane. The enzyme is inactive until bound to activated G
160
What is the function of cAMP?
Its main target is PKA, protein kinase A, which is regulates by separating the regulatory and catalytic subunits
161
What is PKA?
Protein kinase A, which phosphorylates a variety of proteins on Ser or THR residues, using ATP as the energy source
Can phosphorylate amino acids on a receptor and inhibit them
162
G proteins are active for a _____ time
Short
They can quickly respond to changing conditions
163
cAMP is degraded by...
A phosphodiesterase
164
Once a G protein becomes inactive, adenylyl cyclase stops making new cAMP
True
165
What is a GRK?
G-protein-linked receptor kinase, which acts on activated receptors to inhibit their activity, and carry out the phosphorylation on amino acids in the cytosolic domain
165
What is a GRK?
G-protein-linked receptor kinase, which acts on activated receptors to inhibit their activity, and carry out the phosphorylation on amino acids in the cytosolic domain
166
What is IP3?
Inositol-1,4,5-triphosphate
167
What is the role of IP3?
It functions as a second messenger. It's generated from PIP2 when phospholipase C is activated, and it cleaves PIP@ into IP3 and diacylglycerol, both of which are second messengers in a variety of cellular events
168
The role of calcium in cell signalling pathways?
Ca2+ is a part of the IP3 cell signalling pathways, and IP3 binding to receptors on the ER can trigger Ca2+ release. Ca2+ conc. are maintained at low levels through calcium ATPases in the PM and ER. Calcium can bind to effector proteins and alter their activity
169
What is Calmodulin?
It is a protein that mediates many calcium-activated processes in the cell. It has a structure like an arm with a hand at each end, and each end binds two Ca2+
170
Consequences of disruption in G-protein signalling?
Some bacteria cause their diseases through their effects on heterotrimeric G proteins, like Cholera.
When V. Cholera colonizes the gut, it secretes cholera toxin, which modifies G so that it cannot hydrolyze GTP, which alters the salts and fluids in the intestine and can cause death by dehydration.
171
What is receptor affinity?
The relationship between the amount of ligand in solution and the number of receptors occupied
172
What is Kd?
The dissociation constant, which is the amount of free ligand needed to produce a state in which half the receptors are occupied
Receptors with high ligand affinity have low Kd and vice versa
173
Explain Kd = Koff/Kon
"On" is governed by the concentration
"Off" is governed by how tightly the ligand is bound
174
What is Dynamic equilibrium?
The balance between two events (Koff and Kon), and at any given moment, there will be a certain number of unoccupied and occupied receptors
175
What is an Agonist?
They activate the receptor to which they are bound (mimics)
176
What is an Antogonist?
They bing receptors without triggering a change and preventing activation of the receptor (blocks)
177
When is receptor down-regulation?
When receptors are occupied for prolonged periods, that the cell adapts to no longer respond to the ligand
178
How do cells down-regulate receptors?
1. Cells reduce the density of receptors on their cell surface via receptor-mediated endocytosis
2. Cells can adapt to signals by desensitization, alterations to the receptor that lower it's affinity for the ligand and prevent downstream intracellular events
179
What is a common desensitization method?
Phosphorylation
180
What are protein kinase-associated receptors?
Receptors that can also function as kinases, by which they are stimulated by ligand binding. Signalling of the receptor protein kinases is transmitted through a phosphorylation cascade
181
What are growth factors?
Messengers in a serum that stimulate growth; Cultured cells in vitro will not grow unless blood serum is provided
182
What is PDGF?
Platelet-derived growth factor; secreted by platelets as a part of the healing process to stimulate fibroblasts to form new connective tissue. Its receptor is a receptor tyrosine kinase
183
What is the structure of a Receptor Tyrosine Kinase?
A single polypeptide chain with just one transmembrane segment
The extracellular part contains the ligand-binding domain
On the cytosolic side is the tyrosine kinase domain
184
What is autophosphorylation?
When a receptor phosphorylates the same kind of receptor as themselves
185
How is signal transduction initiated?
Upon ligand binding, where receptors form dimers upon ligand binding and phosphorylate each other
Phosphorylated tyrosine residues can be bound by proteins with Src-homology2 (SH2) domains, and can activate phospholipaseC, leading to the production of IP3 and DAG
186
What is Src?
One of the first tyrosine kinases identified. It is regulated by phosphorylation at two sites.
187
What is JAK?
Nonreceptor tyrosine kinase, which binds to the receptor and is activated in response to ligand binding
188
Phosphorylated tyrosine residues can be recognised by...
SH2 domains
189
Why are SH2 domains important?
There are important structural modules for signalling cascades, and proteins with SH2 domains are recruited to proteins that are phosphorylated by tyrosine kinases
190
What is the Kinase cascade?
1. Autophosphorylation of the receptors recruits cytosolic proteins
2. GRB2, which has an SH2 domain that recognizes the phosphotyrosine on EGFR, binds the receptor leading to the activation of Sos
3. Sos stimulates Ras to release GDP and bind a GTP molecule, which activates Ras
4. Activated Ras triggers a series of phosphorylations by Raf
5. MAP kinases are activated
6. MAPKs phosphorylate transcription factors that alter gene expression
7. Once Ras is in its active state, it must be inactivated to avoid continual stimulation of the Ras pathway, which is accomplished by a GAP that facilitates GTP hydrolysis
8/ GDP-bound Ras is now inactive
191
Why is Ras important?
In regulating the growth of cells (it is a small monomeric G protein)
It can bind GDP or GTP, but is only active when bound to GTP
Requires assistance from a GEF (guanine-nucleotide exchange factor) called Sos to acquire a GTP molecule
192
EPK/MAPK can inactivate Ras through a variety of mechanisms to turn off signalling?
True
193
How do we make signalling more efficient?
Scaffolding proteins, where components are assembled into large multiprotein complexes
194
What is the importance of Mating factor?
It signals between cells resulting in large-scale changes to polarized secretion, cytoskeleton, and gene expression?
195
Type I diabetes is caused by...
Loss of insulin-producing cells
196
Type II diabetes results from...
Insulin resistance
197
What is a cytoskeleton?
A network of interconnected filaments and tubules extending through the cytosol
It plays roles in cell movement and division
It is dynamic and changeable
198
What are the major structural elements of the cytoskeleton?
Microtubules
Tubulin
Microfilaments
Actin
Intermediate filaments
Various proteins
199
How do we study receptor function?
Introducing mutations into the receptor: FGFs (Fibroblast growth factors) and their receptor tyrosine kinases... normal FGFRs undergo autophosphorylation in response to ligand binding
200
What are dominant negative receptor mutations?
A mutant that overrides normal function;
Some mutant FGFRs can find ligands but cannot undergo autophosphorylation... these mutant receptors interfere with normal receptor function because they can dimerize with normal receptors
201
What does a dominant mutation in FGFR-3 cause?
A form of dwarfism called achondroplasia
202
What are constitutive mutations?
When mutations cause the receptor to stay switched "on" all the time
203
What is a major class of serine-threonine kinases?
A family of proteins that bind TGFb (Transforming growth factor b) family members
204
What is the TGFb family?
It regulates many cell functions including cell proliferation, programmed cell death, specialization, and key embryonic events
205
Describe the TGFb signalling cascade?
1. Growth factor finds the transmembrane receptor
2. Upon ligand binding, the type II receptor phosphorylates the type I receptor, which then initiates a signal transduction cascade
3. R-Smad is phosphorylated by a complex of anchoring proteins with the receptors
4. Smad 4 forms a ultiprotein complex with phosphorylated R-Smadsl the whole complex can then enter the nucleus
5. In the nucleus, the Smad complex can regulate gene expression
206
What are endocrine hormones?
Hormones that travel from sending to receiving cells via the circulatory system
They are synthesized by endocrine tissues and are secreted directly into the blood stream, with a lifespan ranging from a few seconds to many hours
As they circulate, they encounter their receptors in target tissues
207
What are hormones?
Secreted chemical signals that coordinate the function of cells and tissues over long distances
208
What do steroid receptor proteins do?
Mediate the actions of steroid hormones such as progesterone, estrogen, testosterone, and glucocorticoids
209
What are steroid hormones?
Lipid-based (cholesterol) signalling molecules
The hormone enters the target cell and binds its receptor, triggering a cascade of events that change gene expression
210
How are Bacteria and Archaea structurally similar to Eukaryotes?
The actin-like MreB protein is involved in DNA segregation
The tubulin-like FtsZ protein is involved in regulating division
Crescentin is a regulator of cell shape
211
What are microtubules?
The largest of the cytoskeletal components of a cell
Straight, hollow cylinders of varied length that consist of (usually 13) longitudinal arrays of polymers called protofilaments
212
What are the two types of microtubules?
1. Cytoplasmic microtubules
2. Axonemal microtubules
213
What are cytoplasmic microtubules?
They pervade the cytosol and are responsible for a variety of functions:
- Formation of mitotic and meiotic spindles
- Maintaining or altering cell shape
- Placement and movement of vesicles
214
What are axonemal microtubules?
They include the organized and stable microtubules found in structures such as cilia and flagella
215
What is the axoneme?
The central shaft of a cilium or flagellum, a highly ordereed bundle of microtubules
216
What is a protofilament?
The basic subunit of a protofilament is a heterodimer of tubulin, one a-tubulin and one b-tubulin
They bind noncovalently to form an ab-heterodimer, which does not normally dissociate
217
What is the structure of the a and b subunuts?
They have very similar 3D structure but only 40% amino acid identity
Each has an N-terminal GTP binding domain, a central domain to which colchicine can find, and a C-terminal domain that interacts with MAPs (microtubule-associated proteins)
All dimers in the microtubule are oriented the same way
218
What is to polarity of microtubules?
Protofilaments have an inherent polarity
The two ends differ both chemically and structurally
219
Cytoplasmic MTs are _____ MTs
Singlet, with 13 protofilaments
220
Some axonemal MTs form ______ or _______ Mts
Doublet or triplet
221
What are the characteristics of Doublet and Triplet MTs
They contain one 13-protofilament tubule (A tubule) and one or two additional incomplete rings (B and C tubules) or 10 or 11 protofilaments
222
How do MTs form?
Nucleation: Reversible polymerization of tubulin dimers in the presence of GTP and MG2+
Dimers aggregate into oligomers, which serve as nuclei from which new MTs grow
223
What is elongation?
The addition of more subunits at either end
224
Howdo MTs assemble in vitro?
MT formation is slow at first, which is called the lag phase due to the slow process of nucleation
The elongation phase is much faster; when the mass of MTs reaches a point where the amount of free tubulin is diminished, the assembly is balanced by disassembly; the plateau phase
225
What is the critical concentration?
The tubulin concentration at which MT assembly is exactly balanced by disassembly
MTs grow when the tubulin concentration exceeds the critical concentration and shrink when the concentration is below
226
Do the two ends of a MT differ?
They differ chemically, and one can grow or shrink much faster than the other
This can be visualized by mixing basal bodies
The rapidly growing MT end is the plus end and the other is the minus end
227
What is MT treadmilling?
Addition of subunits at the plus end and removal from the minus end
If the concentration of tubulin subunits is above the critical concentration for the plus end, but below that of the minus end, treadmilling will occur
228
How does colchicine affect the assembly of MT?
It binds to tubulin monomers, inhibiting their assembly into MTs and promoting MT disassembly
229
How does Nocodazole affect the assembly of MT?
It inhibits MT assembly, and its effects are easily more reversed than those of colchicine
230
What are Antimitotic drugs?
They interfere with the spindle assembly and this inhibit cell divison. It is useful for cancer treatment; commonly used for breast cancer
231
How does Taxol affect MT?
It binds tightly to microtubules and stabilizes them, causing a depletion of free tubulin subunits causing dividing cells to arrest during mitosis
232
What are Catastrophins?
They act at the ends of MTs and promote the peeling of subunits from the ends
233
What do Katanins do?
They sever MTs
234
What is the structure of Centrioles?
The walls are formed by 9 pairs of triplet microtubules, oriented at right angles to each other
235
What role do Centrioles play?
They are involved in basal body formation for cilia and flagella
Cells without centrioles have poorly organized mitotic spindles
236
Where do MTs originate from?
MTOC, microtubule-organizing center
Also called the centrosome
In animal cells, the centrosome is associated with two centrioles, surrounded by pericentriolar material
237
How does GTP hydrolysis contribute to MT dynamic instability?
Each tubulin heterodimer binds two GTP molecules, a-tubulin binds one and b-tubulin binds a second
GTP is needed to promote heterodimer interactions and addition to MTs, but its hydrolysis is not required for MT assembly
The GTP bound to the b-subunit is hydrolyzed after the heterodimer is added to the MT
238
MTs grow by ________ and _________ at plus ends
Polymerization and Depolymerization
239
Growing MTs have ___ at plus ends
GTP
240
Shrinking MTs have ___ at plus ends
GDP
241
What stabilizes the MT?
The GTP cap at the plus end
242
If the GTP cap disappears altogether...
The MT becomes unstable and loss of GDP-bound subunits is favored
243
What is Microtubule catastrophe?
A switch from growth to loss of an MT
244
What is Microtubule rescue?
A sudden switch back to the growth phase of an MT
245
What is g-tubulin?
A large ring-shaped protein complex inside of a centrosome
246
What are g-TuRCs?
g-Tubulin ring complexes, which nucleate the assembly of new MTs away from the centrosome
247
Where do MTs grow outwards from?
The MTOC, which a fixed polarity with dynamic growth and shrinkage of MTs occuring at the plus ends
248
What are MAPs?
Microtubule-associated proteins, which bind at regular intervals along a microtubule wall, allowing for interaction with other cellular structures and filaments
Tau causes MTs to form tight bundles in axons
MAP2 promotes the formation of looser bundles in dendrites
249
What are +TIP proteins?
+-end tubulin interacting proteins, which stabilize the proteins that capture and protect the growing plus ends, while decreasing the likelihood that MTs will undergo catastrophic subunit loss
250
What are microfilaments?
The smallest of the cytoskeletal filaments
Best known for their role in muscle contraction
Play critical roles in organelle structure, cell migration and endocytosis, development and maintenance of cell shape
It is the structural core of microvilli
Can assemble to form characteristic structures
251
What is actin?
The building block of microfilaments
Folds into a globular-shaped molecule that can bind ATP or ADP
252
What is G-actin?
Molecules that polymerize to form microfilaments, F-actin
253
What are F-actin microfilaments?
Composed of two linear strands of polymerized G-actin, wound into a helix
254
All actin monomers in the filament have the same orientation?
True (plus and minus end)
255
G-actin polymerizes reversibly into filaments similar to tubulin assembly?
True
256
What are Cytochalasins?
Fungal metabolites that prevent the addition of new monomers to existing MFs (bind the filament)
257
What is Latrunculin A
A toxin that sequesters actin monomers and prevents their addition (bind to the monomers)
258
What is Phalloidin?
Stabilizes MFs and prevent depolymerization (bind to the interface between subunits)
259
What happens after G-actin monomers assemble onto the microfilament?
ATP bound to them is slowly hydrolyzed
260
Growing plus ends have...
ATP-actin
261
Most of the MF is composed of...
ADP-actin
262
What affects the polarity of MFs?
The rapid addition of G-actin at the plus end
263
What are filopodia?
Organized and polarized MF cables with the plus ends toward the tip of the protrusion
More organized than lamellipodia
264
What are stress fibers?
Organized bundles characteristic of cells that adhere tightly to a surface, are needed for attachment
265
What are lamellipodia and filopodia?
Characteristic of cells that crawl and generate force at the leading edge of the cell to allow them to move along a surface
266
Cells regulate ____ and ___ MFs are assembled
Where, how
267
What are actin-binding proteins?
Proteins that control where actin assembles and the organization of the resulting network
Control occurs at the level of nucleation, elongation, severing of MFs, and association of MFs into networks
268
If the concentration of ATP-bound G-actin is high, MFs will...
assemble until the G-actin is limiting
269
What is Thymosin 4?
Binds free G-actin
270
How is the availability of G-actin controlled?
By regulating the amount of it bound to thymosin 4 by profilin
271
What are capping proteins?
They bind the ends of a filament to prevent further loss or addition of subunits
272
What does CapZ do?
Binds to plus ends to prevent loss/addition of subunits
273
What does Tropomodulin do?
Bind to minus ends, preventing loss of subunits
274
What does Selsolin do?
Break up MFs because it can bind to F-actin and sever the filament, cap the plus end to prevent addition or loss of subunits
275
What can we do with the severed filaments?
Crosslink or bundle them to remodel the actin cytoskeleton
276
Gelsolin activity is activated by ___ and inhibited by ___
Ca2+, PIP2
277
What does filamen do?
Form actin networks from loose networks of crosslinked filaments.
Anchors two MFs together where they intersect at a fixed angle
278
What does byfimbrin do?
Tightly bind MFs in a bundle
279
How do proteins link actin to membranes?
Linking proteins, such as Band 4.1 or Ankyrin with Spectrin
They can connect to the PM and exert force on it during cell movement or cytokinesis
280
What is the Arp2/3 Complex?
A complex of actin-related proteins, nucleates new branches on the sides of old filaments
Activated by a family of proteins that includes WASP and WAVE/Scar
281
What is WASP?
Autoinhibited, activated by PIP2, and once activated will activate Arp2/3
282
What are formins?
A protein regulating actin polymerization, move with the end of the growing filament to promote polymerization
283
What are intermediate filaments?
The most stable and least soluble cytoskeletal component
Not polarized
Keratin
Support the entire cytoskeleton
284
What is cell motility?
Movement of a cell or organism through the environment
Movement of the environment past/through the cell
Movement of components in the cell
Occurs at the tissue, cellular, and subcellular level
285
What is cell contractility?
Describes the shortening of muscle cells, a specialized form of motility
286
What are plakins?
Linker proteins that connect IFs, MFs, and MTs
287
What is plectin?
A plakin found at sites where IFs connect to MFs and MTs
288
What are intercalated discs?
Joins heart cells from end to end
Have a high concentration of gap junctions, so waves of depolarization spread easily from one cell to the next
289
What is smooth muscle?
Responsible for involuntary contraction in various tissues
Contractions are relatively slow and of greater duration than in skeletal or cardiac muscle
290
What is the structure of smooth muscle?
Long and thin with pointed ends, no striations
Dense bodies, plaque-like structures
Bundles of actin filaments are anchored to the dense bodies in a crisscross pattern, cross-bridges form in an irregular pattern
291
What are integrins?
Transmembrane proteins:
Outside the cell: attached to the extracellular matrix proteins
Inside the cell: connected to actin filaments via linker proteins
292
What are adhesions/focal contacts?
Integrin-dependent attachments
293
What is Directional migration?
Occurs through the formation of protrusions predominantly on one side of a cell
294
What is chemotaxis?
Whena cell moves in response to a chemical gradient
295
What are Chemoattractants?
When cells move toward a higher concentration of the diffusible molecules
296
What are Chemorepellants?
When cells move toward a lower concentration of the diffusible molecules
297
Binding of the molecules to cell surface receptors leads to...
Corresponding cytoskeletal changes
298
What does activation of the Rho pathway result in?
Formation of stress fibers
299
What does Rac activation result in?
Extension of lamellipodia
300
What does Cdc42 activation result in?
Formation of filopodia
301
How does a smooth muscle contract?
1. In response to a nerve or hormonal signal, extracellular calcium enters the muscle cell, activating Calmodulin
2. The calcium-Calmodulin complex binds to MLCK, activating it and triggering myosin light-chain phosphorylation
3. Phosphorylation leads to a conformational change in myosin, promoting its assembly into filaments and activates the cross-bridge cycle
4. As the calcium levels in the muscle cell fall, MLCK is inactivated
5. Myosin light-chain phosphatase removes the phosphate from the myosin light chain and the muscle cell relaxes
302
What is cell crawling?
Movement of most cells in animals through MFs
Involves: extension of a protrusion, attachment to a substrate, and generation of tension which pulls the cell forward
303
How do crawling cells generate force and movement?
Cells extend protrusions at their front/leading edge, and by actin retrograde flow, MFs move toward the rear of the protrusion as it extends
304
What is retrograde flow?
Flow resulting from actin assembly at the growing protrusion and rearward translocation of filaments toward the base
305
How do cells attach?
New sites of attachment are formed at the front of the cell, and contacts at the rear must be broken
306
What are attachment sites?
Complex structures involving a number of proteins including integrins
307
How do cells contract?
Under the control of Rho, nonmuscle myosin II at the rear of the cell is activated
The cell body is squeezed forward and releases attachments at the rear
308
For new movement to occur, new attachments must be balanced by...
Loss of old ones
309
What is phosphatidylinositol-4,5-bisphosphate (PIP2)?
Binds to profilin, WASP, CapZ, gelsolin and other proteins
310
What are the Rho GTPases?
Rho, Rac, Cdc42
Monomeric G proteins
311
How are Rho GTPases regulated?
They are stimulated by GEFs through the exchange of bound GDP for GTP
GAPs inactivate Rho GTPases bycausing them to hydrolyze their bound GTPs to GDP
GDIs sequester inactive Rho GTPases in the cytosol
312
What is the Sarcoplasmic reticulum?
Has calcium ATPases to pump calcium into the SR
313
How are calcium levels controlled?
By nerve impulses from motor neurons, calcium release into the cytosol of a muscle cell triggers contraction, for muscles to relax, calcium levels must decrease
314
IF proteins are ___ rather than globular
Fibrous
315
What is IF structure?
All have an homologous central rodlike domain conserved in size, secondary structure, and in sequence
Flanking the central helical domain are N- and C- terminal domains that differ greatly among IF proteins
316
Why are IFs important structural determinants?
Because they are thought to have a tension-bearing role
Less dynamic than MFs and MTs but are not static structures
317
Cell architecture depends on...
The unique properties of all the cytoskeletal elements working together
318
MTs _____ binding when a cell is compressed
Resist
319
MFs serve to ____ tension and force
Generate
320
IFs are ___ and can withstand tensile forces
Elastic
321
MTs and MFs provide a scaffold for motor proteins, or mechanoenzymes to...
Produce motion at the molecular level
322
What is the structure of cilia and flagella?
Axonemes have a characteristic 9+2 pattern, with 9 outer doublets and 2 MTs in the center, the central pair
Each outer doublet of the axoneme consists of one complete MT (the A tubule) and one incomplete MT (the B tubule)
The A tubule has 13 protofilaments, whereas the B tubule has 10 or 11, the tubules of the central pair are both complete
Each A tubule has a set of sidearms that project from each of the outer doublets; these consist of axonemal Dynein
323
What is the role of Axonemal dynein?
* Axonemal dynein is involved in the sliding of MTs against each other, which bends the axoneme
* The dynein arms occur in pairs, one inner and one outer arm
324
What are primary cilia?
Primary cilia are present on almost all cells and serve as sensory structures
These have a “9+0” structure, i.e., lacking the central pair
Primary cilia are also important in development; defects in them can result in disorders such as deafness and left-right asymmetry reversals
325
What are myosins?
Myosins are ATP-dependent motors that exert force on actin filaments
Currently there are 24 known classes of myosins
All have at least one polypeptide chain called the heavy chain, with a globular head group attached to a tail of varying length
326
What are Myosins function?
* Muscle contraction
* Cell movement
* Phagocytosis
* Vesicle transport
Type II myosins are the best understood
They have two heavy chains (each with a globular head, a hinge region, a rodlike tail) and four light chains
They use ATP hydrolysis to cause actin filaments to slide past myosin molecules, resulting in contraction of a cell or group of cells
the functions of myosin?
327
What is the structure of myosin?
The globular head binds actin and uses the energy of ATP hydrolysis to move along the filament
Most move toward the plus-end but myosin VI is an exception
The tail region varies among classes of myosin, which vary in the types of molecules or structures they can bind
328
What is kinesin?
involved in ATP-dependent transport toward the plus ends of MTs, called anterograde transport
329
What is dynein?
moves particles (cargo) toward the minus ends of MTs, called retrograde transport
330
Proteins and neurotransmitters produced in the cell body must be transported....
to the nerve ending...diffusion is too slow.
331
What is fast axonal transport?
involves movement of vesicles and organelles along MTs
Organelles can be observed moving along filaments at rates of about 2 m/sec (~80 minutes per cm).
332
What is the structure of kinesin?
Kinesins consist of three parts
– A globular head region that attaches to MTs
– A coiled helical region
– A light-chain region involved in attaching the Kinesin to other proteins or organelles
Kinesins move along the MT in 8-nm steps; the movement is coupled to ATP hydrolysis
Kinesin movement looks like “walking” with the two globular head domains taking turns as the front foot
Each Kinesin molecule exhibits processivity
It can move long distances along a MT before detaching from it
Front foot is empty (apo) and bound to β tubulin
Back foot is bound to ADP and not bound to tubulin
ATP binding in the front foot forces the back, ADP-bound foot forward (force)
ATP hydrolysis in (the now) back foot promotes 1) Pi release and 2) the now ADP-bound foot to release tubulin
At the same time, binding of the ADP-bound front foot binds tubulin which forces ADP release
333
What does Cytoplasmic Dynein do?
Move toward the minus ends of MTs, associated with Dynaction, which helps link it to cargo
334
What does the sliding-microtubule model suggest?
The sliding filament model was proposed in 1954
According to the model, muscle contraction is due to thin filaments sliding past thick filaments, with no change in length of either. That sliding of MTs relative to each other is converted into localized bending because the doublets are connected to the central pair and to each other
335
What is the role of calcium in contraction?
The regulatory proteins tropomyosin and troponin regulate myosin binding
When the calcium concentration is low, tropomyosin blocks the myosin binding sites on the actin filament
At higher concentrations, calcium binds TnC of the troponin complex, causing tropomyosin to shift, and allowing myosin to bind
336
How are cross-bridges formed?
Cross-bridges are formed from links between the F-actin of thin filaments and myosin heads of thick filaments
Cross-bridges must dissociate repeatedly during contraction; each cycle of cross-bridge formation causes thin filaments to slide past thick filaments
The result is shortening of sarcomeres and muscle fiber contraction
337
What does actinin do?
Keep actin filaments bundled into parallel arrays
338
What does CapX do?
Maintain the attachment of the plus ends to the Z line and caps the actin in the filaments
339
What does Tropomodulin do?
Binds the minus ends of the filaments to maintain stability
340
What does Nebulin do?
Defines thin filament length and helps anchor it to the Z line
341
What does Myomesin do?
It is present at the H zone and helps anchor it to the Z line
342
What does Titin do?
Attaches the thick filaments to the Z lines and keeps think filaments in the correct position relative to thin filaments during contraction
343
Explain Cross-bridge formation:
Structural states of myosin during the contractile cycle. Without bound nucleotide, myosin is strongly bound to actin (rigor state). ATP binding dissociates the complex actin-myosin. ATP is then hydrolyzed to ADP+Pi. There is a swing of the lever arm (green). Myosin can rebind to actin, release ADP+Pi and produce force by returning to the original state where myosin is again strongly bound to actin without nucleotide bound.
344
What are cilia?
are about 2–10 m long and occur in large numbers on the surface of ciliated cells
They occur in both unicellular and multicellular eukaryotes
Cilia display an oarlike pattern of beating, generating a force parallel to the cell surface
345
What are flagella?
move cells through a fluid environment
They are the same diameter as cilia, but usually much longer (up to 200 m)
They are limited to one or a few per cell and move with a propagated bending motion
346
Describe the axoneme?
Cilia and flagella share a common structure, theaxoneme
It is connected to a basal body and surrounded by an extension of the cell membrane
Between the axoneme and basal body is a transition zone in which the MTs take on the pattern characteristic of the axoneme
347
What are thin filaments?
Thin filaments interdigitate with the thick filaments
Thin filaments contain three proteins: F-actin, intertwined
with tropomyosin and troponin
One troponin complex associates with each tropomyosin
Together they constitute a calcium-sensitive switch that activates contraction in striated muscle
348
Why are Z lines important?
The actin in thin filaments is oriented so that all the plus ends are anchored at Z lines
Myosin II moves toward the plus ends, so the thick filaments move toward the Z lines during contraction
349
Each thick filament...
consists of hundreds of molecules of myosin, oriented in opposite directions in the two halves of the filament
350
What is the difference between Kinesin and Myosin?
Myosin II is an efficient motor that “walks” along actin like Kinesin walks along microtubules
Both have two heads that walk along a protein filament, and both use ATP hydrolysis to change their shape
Kinesins operate alone or in small numbers to transport vesicles over large differences
* Myosin II molecules move short distances but operate in large arrays, in some cases billions of motors working together to mediate muscle contraction
351
What is striated muscle?
The filaments in skeletal muscle are aligned,
giving myofibrils a pattern of alternating dark and light bands (e.g. striated muscle)
Dark bands are A bands and light bands are
I bands
The lighter region in the middle of each A band is called the H zone; the M line runs down the center
The M line contains myomesin, a protein that links myosin filaments together
In the middle of each I band is a dense Z line; the distance from one Z line to another defines a sarcomere
352
What is involved in Muscle contraction?
Muscle contraction is the most familiar example of mechanical work mediated by intracellular filaments
Much of what is known about contractile processes is based on studies involving skeletal muscle
Each muscle fiber contains numerous myofibrils, each of which is divided along its length into repeating units calledsarcomeres
Each sarcomere contains bundles of thin filaments (containing actin, troponin and tropomyosin) and thick filaments (containing myosin)
353
Why are MT motors important?
MT motors are important for dynamically shaping the complicated endomembrane system
For example, ER membrane extensions can be moved along MTs
The vesicles to and from the Golgi complex are carried by MT motors on microtubule tracks
354
What is the importance of Cytoplasmic dynein?
ATP binding and hydrolysis causes the dynein to take a step forward
Pi release provides the force – remodeling of the complex pulls the cargo closer (towards the minus end)
Dynein hops and pulls
