Test 4 Review Flashcards
Which happens when a cell surface receptor activates a G protein?
the alpha subunit exchanges GDP for GTP
When cells respond to an extracellular signaling molecule they most often convert the information carried from one form to another, this is a process called?
signal transduction
Microtubules are important for transporting cargo in nervel cell axons in Figure I shows two cargo molecules traveling in opposite directions, which is true?
all of the above
What shortens during muscle contraction?
sarcomeres
When the hromone insulin is secreted into the bloodstram, what form of cell to cell signalling is being used?
endocrine
Figure 2 shows the leading edge of the lamellipodium, which is true?
all of the above
Many of the extracellular signalling molecules that regulate inflammation are released locally at the site of the infection. What form of extracellular signalling is this?
paracrine
Monomer that binds to ATP
Actin
What includes keratin and neurofilaments?
intermediate filaments
What can be connected by desmosomes?
intermediate filaments
What is used in eukaryotic cilia?
microtubules
True/False
Each type of extracellular signaling molecules elicits similar responses in different target cells
False
Cell movements require coordination of the events in cell life. Which is required for cell motility?
All of the above
Where are lamins found?
nucleus
Where are neurofilaments found?
nerve cells
Where are vimentins found?
the nucleus
Where are keratins found?
connective tissues
Most extracellular signal molecules act on cell-surface receptors rather than intracellular receptors because>
too hydrophobic/too large
The Ras protein is a GTPase that functions in many growth factors signaling pathways with GTP bound it transmits downstream signal for cell proliferation inactive with GDP bound and no signal is transmitted.
Mutations for Ras are frequently found in cancers. What would contribute to uncontrollable growth in cancers?
A change that decreases the rate of hydrolysis of GTP by Ras
True or False:
When studying signal transduction pathways in lab, mutant transmemberane protein receptors can be synthesized to determine exactly where intracellular signaling molecules bind
true
Figure 3 shows normal signalling with Ras downstream of RTK and and you examine a cell line with a constituively active Ras. Which of these will turn of signalling?
Addition of any drug that blocks protein y from interacting with its target
Which is important for flagellar movement?
All of the above (microtubules, Dynein, ATP)
Figure 4, shows intracellular signal pathways are highly connected. Which of these is false about the pathway
cyclic AMP is activated only when RTK is active and not when GPCR is active
Which would enhance microtubule polymerization?
addition of anything that inhibits hydrolysis of GTP carried by tubulin dimers
True/False:
In the Notch signalling pathway the tail of the surface receptor travels to the nucleus where is regulates the transcription of specific genes
True
Certain mutant RAS proteins found in cancers can’t hydrolyze GTP to GDP and therefor?
Can’t turn themselves off
Acetylcholine bonds to the GPCR on heart muscle which makes the heart beat more slowly. Receptors stimulated on the G protein opens a K+ channel which will repress/weaken?
all of the above
What is the main function of intermediate filaments?
enable cells to withstand significant mechanical stress when stretched
GTP binding proteins that act as molecular switches inside the cell?
activate when GTP is bound
T/F
Subunits of microtubules and actin filaments are globular proteins, wheras those of intermediate filaments are themselves filamentous
True
T/F
enzyme coupled receptors are transmembrane proteins that display their ligand binding domains on the outer surface of the plasma membrane
True
What grows out from a centrosome towards the cell membrane preiphery
microtubules
Which component of a G proetin can activate target proteins in an intracellular signalling pathway
alpha subunit and beta gamma subunit
T/F
Serine/theronine kinases remove phosphate groups from phosphoroylated serines and theronines
False
Hydrolysis of GTP to GDP carried out in microtubules?
allows for behavior of microtubules called dynamic stability
Following binding of an extracellular signal molecule, RTKs are activated by dimerization of respective ligands which allows?
Each polypeptide chain to cross phosphoylate the other chain in the dimer specific tryosines in its cytoplasmic tail
Kinesin and dynein motor proteins each use the energy of _______ to power movements, _______ along microtubules.
ATP hydrolysis; in a single direction
In a centrosome which structures serve as a nucleation site for formation of microtubules?
Y tubulin rings
T/F
The concentration on actin monomers is high in the cytosol but monomer sequestering proteins that bond to actin monomers can prevent them from polymerizing into fully mature actin
True
GPCRs are referred to as 7 pass membrane receptors because:
Polypeptide chain crosses the lipid bilayer 7 times
Phosphorylates tyrosines on activated RTKs?
Serve as binding sites for a variety of intracellular signalling proteins
Which subunit of G protein is not tethered to the membrane by a lipid bilayer?
beta subunit
T/F some intracellular signalling proteins serve to integrate incoming signals in these pathways cellular response is achieved only when both/all activating signals are presents
true
T/F
The cytoskeleton gives a cell its shape and allows the cell to organize its internal components
True
What is included in the cytoskeleton?
Intermediate filaments
microtubules
actin filaments
All of the above
T/F
The cytoskeleton is directly responsible for large-scale movements such as crawling of cells along a surface, contraction of muscle cells, changes in cell shape, movement of sperm, segregation of chromosomes into daughter cells during cell division
True
What forms the strong, durable networks in the cytoplasm of the cell with sheet-like connections?
Intermediate filaments
How are the intermediate filaments in each cell connected?
through desmosomes
Desmosomes allow?
Forceable activites, and mechanical stress without them the cell would lyse
What does the intermediate filament protein monomer consist of?
a central rod domain with globular regions at either end
Pairs of monomers form?
a dimer
Two dimers form a ?
staggered tertramer
T/F
Tetramers can pack together end to end and assemble a helical array
True
An array contains ________ strands of tetramers that twist together to form the final ropelike intermediate filament.
eight strands of tetramers
A staggared tetramer consists of?
two dimers that sit on top of each other, staggered
What is a lamina?
A lamina is formed from dquare lattice of intermediate filaments composed of lamins
What builds in the bundling of intermediate filaments and links these filaments to other cytoskeletal protein networks
Plectin
How do microtubules begin?
as globular proteins
From what structures do intermediate filaments extend from?
an organizing center such centrosome, a spindle, or basal body of a cilium
T/F
Microtubules are long and relatively stiff hollow tubes of protein that can rapidly disassemble in one location and reassemble in another
True
The _____ end will always be bond to the organizing center and the ______ end is for polymerization.
the minus end will always be bound to organizing center and the plus side is for polymerization
Microtubules are hollow tubes of ______.
tubulin
T/F
A microtubules has a definite sturctural polarity
True
T/F
Tubulin polymerizes from nucleation sites of a centrosome
True
What does a centrosome consist of ?
A matric of protein containing the gamma-tubulin rings that nucleate microtubule growth
What does a centrosome consist of in animal cells?
A pair of centriles, each made of a cylindrical array of short microtubules
Gamma tubules bind with?
The minus end of a microtubule
Tubulin dimers carrying ____ bind more tightly to to one another than do tubulin dimers carrings ______.
Tubulin dimers carrying GTP bind more tightly to to one another than do tubulin dimers carrings GDP
Microtubules that have freshly added tubulin dimers at their end with GTP do what?
Keep growing
When microtubule growth is slow, the subunits in this GTP cap will hydrolyze their GTP to GDP before freash subunits loaded with GTP have time to bind, what happens next?
The GTP cap is thereby lost, the GDP-carrying subunits are less tightly bound in the polymer and are readily released from the free end, so that the microtubule begins to shrink continuously.
A newly formed microtubule will persist only if?
both its ends are protected from depolymerization
T/F the minus end of microtubules are protected by organizing centers, while the plus ends are initially free but can be stablized by other proteins
True
A capping protein allows the cell to?
move and change
Microtubules transport what along a nerve cell axon?
cargo
In nerve cells, all the microtubules are?
pointed in the same direction with their plus ends toward the axon terminal
The outward traffic from a nerve cell is driven by proteins called?
kinesins
The inward traffic in the reverse direction is driven by?
dyneins
Dynenins, carrying inward traffic, takes material from the?
tip of the axon
materials are ingested here or produced by breakdown of proteins and other molecules
How do motor proteins move along microtubules?
by using their globular heads
The two motor proteins which move along microtubules belong to?
The protein familes of kinesins and dyneins
When hearing kinesin, you should think of the?
plus end, because the move towards the plus end of the microtubule
When hearing dynenins you should think of?
the minus end, because they move towards the minus end
The globular head of kinesin and dynein are enzymes with?
ATP-hydrolyzing (ATPase) activity
T/F
A orderly transition among the three conformations is driven by the hydrolysis of bound ATP so that the motor protein is “walking” along the microtubule
True
The tail of a motor protein determines what?
What type of cargo that the protein transports
What are cilia?
hairlike structures that are covered by the plasma membrane
What is the repetitive cycle of movements which is how a cilia beats?
It has a repetitive cycle that consists of a power stoke and a recovery stroke
What occurs during the fast power stroke of a cilium?
The cilium is fully extended and fluid is driven over the surface of the cell
What occurs during the slower recovery stoke of a cilium?
The cilium curls back into position with minimal disturbance to surrounding fluid
How do flagella propel a cell?
With a repetitive wavelike motion
T/F
Flagella are designed to move the entire cell and instead of getting a current, they propagate regular waves along their length that drive the cell through liquid.
True
Microtubules in cilium or flagella are arranged in a what array
9+2 array
Describe the 9+2 array
There are 9 outer tubules that carry two rows of dynein molecules
In a living cell, how does the 9+2 array produce the force for ciliary beating?
the dynein heads periodically make contact with the adjacent microtubules and move it along, producing the force for ciliary beating
What is the cytoplasm made up of>
intermediate filaments, microtubules and actin filaments
What are the types of intermediate filaments in the cytoplasm?
keratins, vimentin and neurofilaments
Microtubules are _________ formed by the polymerazation of _______ _______.
Microtubules are hollow tubes formed by the polymerization of tubulin dimers.
The minus end of a microtubule is embedded in?
the organizing and processing center
Dynamic instablility describes?
how many of the microtubules in a cell are in a dynamic state which they alternate between a growing state and a shrinking state
T/F
Each tubulin dimer has a tighly bound GTP that is hydrolyzed to GDP after tubulin has assembled into a microtubule
True
When GTP hydrolyzes, it reduces the affinity of the subunit and decreases the stablilty of the polymer. What does the cause?
the polymer to disassemble
Microtubule stabilizing and capping allows the cell to do what?
re-orient and re-polarize
What type of actin filaments are stable (AKA don’t move)
Microvilli on the epithelial cells of the small intestine, inner ear, tongue and mouth
What type of actin filaments basically help absorb tension/receive force?
Contratile bundles in the cytoplasm
What are lamellipodia and filopodia?
Sheet-like protrutions from leading edge of a moving cell
Actin filaments are?
thin flexible protein threads
What is the structural makeup of an actin filament?
a two-stranded helix with a twist repeating every 37nm
What does ATP hydrolysis do the the stability of the actin polymer?
decreases the stability
Soon after assembly of actin into the growing filament, what occurs to the ATP in the actin monomer?
it is hydrolyzed to ADP as soon after assembly
What is ‘treadmilling’ in an actin filament?
The actin filament will grow on the plus end and shrink on the minus end
When does treadmilling occur in the actin filament?
it occurs when ATP-actin adds to the plus end of a filament and simultanously looses ADP from the minus end
What controls the behavior of actin?
Actin-binding proteins
How does the actin-cortex affect forward motion of the cell?
Actin is polymerized at the leading edge of the cell and pushed the plasma membrane forward and forms new regions of the actin-cortex
New points of anchorage are made between the actin filaments and the surface that the cell is crawling
contraction at the rear then draws the cell body forward
This process continues, moving the cell forward
T/F
The nucleation of new actin filaments is mediated by actin-releasing proteins attatching to the sides of pre-existing filaments.
True
When actin is moving the the lamellipodium forward, the actin filaments are protected how?
By capping proteins
What helps to drive the elongation of actin filaments?
Formins
How do formin dimers promote filament growth?
They promote filament growth by holding on to one of the two actin subunits exposed at the plus end and pulls in a new actin monomer
What is myosin-1?
a singular globular head and a tail that attaches to another molecule or organelle in the cell
What does the structural arrangement of myosin-1 do to move?
It allows the head domain to move a vesicle relative to an actin filament or and actin filament and the plasma membrane closer together
T/F
Myosin-II molecules can associate with one another to form myosin filaments
True
What is the structural arrangement of a myosin-II molecule?
It has two globular heads and a coiled-coiled tail
Myosin-II mediates the __________ of an actin filament bundle
shortening
How does myosin-II mediate the shortening of actin filaments?
The small bi-polar filaments composed of myosin-II moleucules can slide actin filaments over each other, thus mediating local shortening of an actin filaments
How are myosin-I and myosin-II similar?
Both head groups walks toward the plus end of the actin filament in contacts
What are the structural components of a muscle cell?
A skeletal muscle cell is packed with myofibrils, each of which consists of a repeating chain of sarcomeres
Myofibrils contain what?
Actin and myosin filaments that are arranged in a highly organized structure with a striped appearance
What are the contractile units of muscle?
Sarcomeres
Where are the attachment points for actin filaments in a sarcomere?
Z-disks on either end of the sarcomere
How do muscles contract?
by a sliding-filament mechanism
T/F
During contraction, the actin and myosin filaments slide past each other without shortening, the sliding motion is driven by the myosin heads walking towards the plus end of the adjacent actin filament
True
Name the steps in which a myosin head walks towards a actin filament
Attachment- myosin head missing a nucleotide is locked tightly onto an actin filament in a rigor conformation
Released-ATP binds to head of myosin and immediatly causes conformational change of the actin-binding site (this allows it to move along the filament)
Cocked-The cleft closes around the ATP triggering a shape change that causes head to be displaces along filament. Hydrolosis of ATP occurs but ADP and P remain tightly bound
Force-Generating: A weak binding of myosin head to a new site on the actin filament causes release of P along with tight binding to the head of actin. This triggers the power stroke (looses ADP and P, which returns the head to orginal conformation)
Attached: At the end of the cycle, myosin head is again locked tightly to actin filament in rigor configuration
What ion is involved in skeletal muscle contraction?
Ca2+
T/F
A CA2+ release channel in the sarcoplasmic reticulum membrane is thought to be opened by activation of a voltage gated Ca2+ channel in T-tubule membrane
True
Skeletal muscle contraction is controlled by?
troponin
When the Ca2+ binds to troponin, what occurs?
The troponin moves the tropomyosin that otherwise blocks the interaction of actin with the myosin heads
Signal transduction is?
the process of converting an extracellular signal into a intracellular signal to elicit a specific cellular response
What is the typical communication between cells?
the signalling cell produces a signal molecule that is detected by a target cell
How to target cells recognize and respond to a signal cell?
via receptor proteins on the cell surface
What type of cell signalling is sometimes refered to as ‘global signalling’ and is carried in the blood to distant target cells?
Endocrine
What type of signalling is transmitted along acons to remote target cells and can be referred to as ‘action potentials’?
neuronal
What type of signalling is released by cells into extracellular fluid and act locally?
Paracrine
What type of signalling involves direct communication through cell-cell contact?
Contact-dependent signalling
Cells that produce hormones are?
endocrine cells
When action potentials reach the axon terminal, electrical signals get converted into chemical signals called ____________ and these diffuse across the ________ _______ to reach the membrane of the target cell.
neurotransmitters; synaptic gap
Signal molecules that regulate inflammatory responses work in what manner?
Pacrine signalling
Cancer cells can also promote their own survival through a type of paracrine signalling called?
autocrine signalling
Autocrine signalling is?
local mediators that are produced by cells themselves to promote survival or cell proliferation
How does contact dependent signalling work?
cell makes direct physical contact through signal molecules lodged in the plasma membrane of the signalling cell and receptor proteins embedded in the plasma membrane of the target cell
What are the two categories of Extracellular signals?
Those that are too large or too hydrophobic to cross plasma membrane:
-these must rely on membrane receptors
those that are small enough or hydrophobic enough to diffuse across the plasma membrane:
-they then bind to intracellular enzymes or intracellular receptor proteins
Extracellular signals that are too big/hydrophobic enough to diffuse have to enter the cell by what steps?
receptor cell performs 1st signal transduction step by binding to extracellular signal (primary messenger) and then generates new intracellular signal (secondary messenger)
What is the ‘molecular relay race’?
After inital intracellular signal is created, the signals continue to get passed ‘downstream’ until the response of the cell has been completed
What are the purposes of the intracellular signalling pathways?
hint-4
1-relay signal
2-amplify signal received
3-receive signals from multiple intracellular signaling pathways and integrate them
4-distribute the signal to more than one signaling pathway or effector proteins
Intracellular signalling proteins can also function as?
*hint-can halt signal pathway
Molecular switches
Molecular switches are?
molecular switches can function to allow signals to switch between inactive and active states
What are the proteins that can act as molecular switches?
kinases: Serine/threonine kinases, Tyrosine kinases
GTP binding proteins
What are the three classes of surface receptors?
1) ion channel-coupled receptors
2) G-Protein Coupled Receptors (GPCRs) * fun fact: targets ~50% of known drugs
3) Enzyme coupled receptors
Ion-Channel Coupled receptors?
always allow flow of ions across plasma membrane
Basically, upon stimulation, these channels will open to relay signal
How to GCPRs work?
Activates membrane-bound trimeric GTP binding proteins which the activate either a enzyme or a ion channel in plasma membrane
A GPCR has what type of structure?
a GPCR is a single polypeptide chain that is a seven pass transmembrane receptor protein
When a signal molecule the GCPR receptor does what?
undergoes a conformational change that enables it to activate a G protein on the underside of the plasma membrane
What is each G-protein composed of?
an alpha, beta and gamma subunit
When an extracellular ligand binds to the receptor, the receptor activates a G protein by causing the?
alpha subunit to release GDP, and exchange it for GTP
T/F
Unlike GPCRs, enzyme coupled receptors are transmembrane proteins that display their ligand-binding domains on the outer surface of the plasma membrane
True
The cytoplasmic domain of a enzyme coupled receptor either acts as?
an enzyme itself or forms a complex with another protein that acts as an enzyme
What do enzyme coupled receptors do?
respond to growth factors, regulate cell growth, proliferation, differation and survival
Also mediate and direct rapid configerations of the cytoskeleton to control cell shape and movement
Abormalities in signaling via enzyme coupled receptors could have a major role in?
cancer developement
A large class of enzyme coupled receptors called _______ ______ _____ stimulates the assembly of intracellular signaling complexes.
receptor tyrosine kinases (RTKs)
RTKs stand for?
receptor tyrosine kinases
The binding of a signal molecule to the extracellular domain of an RTK causes?
two receptors to bind with a dimer
What does the action of two RTK receptors binding with a dimer result in?
Dimerization results in the activation of kinases and enables them to phosphorylate their tyrosines.
Each phosphorylated tyrosine serves as a binding site for a different intracellular signaling protein which relays the signal to the cell’s interior
One of the key players in RTK signalling complexes is a _____ a small GTP binding protein that is bound by a lipid tail to the cytoplasmic face of the plasma membrane
Ras
30% of human cancers contain activating mutations in what genes?
Ras
How do the activating mutations in Ras genes in cancerous cells affect the Ras genes?
they led to an inactivation of the GTPase activity of Ras so that the Ras cannot shut itself off
In it’s active state, Ras promotes the activation of a phosphorylation cascase in which a series of serine/threonine protein kinases phosphorylate and activate one another. What is activated at the end of this cascade?
A MAP-kinase signalling molecule
Map kinase phosphorylates various downstream signalling or effector proteins including other?
protein kinases, transcription regulators the control gene expression
Insulin-like growth factor acts through _____.
RTKs
One crucial signalling pathway that RTKs activate to promote cell growth and survival relies on?
phosphoinositide 3-kinase (PI 3-kinase)
What does PI 3-Kinase do?
once activated, it phosphorylates a membrane-associated inositol phospholipid which recruits a protein kinase called Akt that is activated by protein kinase 1 and 2
Activated Akt does what?
promotes cell survival by inactivating the signal protein called Bad
stimulates cells to grow in size by activating Tor
In its unphosphorylated state, what does Bad do?
promotes apoptosis
What does Tor do?
simulates protein synthesis and inhibits protein degradation
What anticancer drug slows cell growth and proliferation by inhibiting tor?
rapamycin
The notch receptor itself is?
A transcription regulator
