10 - Signaling Pathways Directing Cell-Polarization II Flashcards
(136 cards)
1
Q
How is cell polarization characterized?
A
By molecular segregation
2
Q
How is a functional polarization achieved?
A
By having molecules that perform a specific function segregated in space
3
Q
What is the purpose of model organisms?
A
Study broad biological principles (such as cell signaling)
4
Q
What are some examples of model organisms?
A
Drosophila melanogaster (fruit fly), C. elegans (nematoad), zebrafish, and Mus musculus (mouse)
5
Q
What model organism is the most critical for human?
A
Rodent models
6
Q
Why are rodent models the most critical for humans?
A
There is a direct implication between rodent and human
7
Q
What are the advantages of using model organisms?
A
Can be grown easily in the lab, relatively cheap, and easily manipulated
8
Q
What does “in vitro” mean?
A
In the glass / test tube
9
Q
What kind of study involves isolated cells in a test tube?
A
In vitro
10
Q
What are the advantages of an in vitro study?
A
It is easily manipulated and cheaper
11
Q
What are the disadvantages of an in vitro study?
A
It is a reduced system (does not reflect natural conditions fully)
12
Q
What does “in vivo” mean?
A
In the living
13
Q
What kind of study involves doing experiments in the model organism?
A
In vivo
14
Q
What are the advantages of an in vivo study?
A
The conditions reflect the natural environment
15
Q
What are the disadvantages of an in vivo study?
A
They are harder to manipulate (not easy or cheap)
16
Q
What technique is a “combination” of in vivo and in vitro?
A
Ex vivo
17
Q
What is an ex vivo study?
A
Experiments are done in isolated tissues
18
Q
What is the advantages of an ex vivo study?
A
Can easily manipulate the system, but still has some local conditions based on the surrounding cells in the tissue (communication)
19
Q
True or false: ex vivo studies perfectly mimic the natural environment
A
False: it only mimics it slightly (based on the tissue)
20
Q
What cells serve as models for cell polarization?
A
Neurons and epithelial cells
21
Q
What are epithelial cells?
A
Cells that form tight boundaries (connected sheets)
22
Q
What do epithelial cells do?
A
Line surfaces and cavities of an organism
23
Q
What does the function of epithelial cells depend on?
A
The ability to develop and maintain polarized structures
24
Q
What are the distinct domains of an epithelial cell?
A
Apical and basolateral domains
25
What separates the apical and basolateral domains?
Tight junctions
26
True or false: the apical domain is morphologically different from the basolateral domain
True: the apical domain has microvillae structures, while the basolateral domain does not
27
What is the structure of the apical domain?
Microvillae structures
28
What are microvillae?
Actin protrusions on the apical domain of epithelial cells
29
What is the function of microvillae?
Increase surface area for digestion / absorption
30
What domain occupies the majority of the epithelial cell?
The basolateral domain
31
True or false: the apical domain is biochemically different from the basolateral domain
True: the apical domain and basolateral domain have different cell receptors
32
How are epithelial cell domains morphologically distinct?
The apical domain has microvillae, while the basolateral domain does not
33
How are epithelial cell domains biochemically distinct?
The apical and basolateral domains have different cell surface receptors
34
What do tight junctions do?
Act as a barrier for water and solutes, and restrict movement of cell surface proteins between apical and basolateral domains
35
What is the significance of tight junctions acting as a barrier for water and solutes?
Create distinct extracellular spaces between apical and basolateral domains
36
What is the significance of tight junctions restricting lateral movement of cell surface proteins?
Prevent lateral diffusion to keep the distinct compositions of the apical and basolateral domains
37
What is needed for proper epithelial cell polarization?
1. Proper cell domains have to form (morphologically and biochemically)
2. The junctional complexes have to form
3. Proper cell-surface receptors need to be trafficked to the proper domain, and maintained there
38
What is the most basic building block of brain circuitry?
The polarized neuron
39
What is the name for a cell body for a neuron?
The soma
40
What does the soma contain?
Cytoplasm, nucleus, etc.
41
What are the different compartments of a neuron?
The somatodendritic component, and the axon component
42
What is the morphology of the dendrites?
Short, stubby, branched protrusions
43
What is the morphology of the axon?
One long process
44
What is the function of the axon?
To transmit electrical / biochemical neuronal signals
45
What is the function of the dendrite?
Receive and compute signaling information from different axons
46
How are dendrites and axons (generally) different?
In their morphology, molecular composition, and function
47
What happens in stage 1 of in vitro neuronal development?
Cytoskeletal protrusions
48
What are the characteristics of the cytoskeletal protrusions in stage 1 of in vitro neuronal development?
Random and unassigned
49
When does stage 1 of in vitro neuronal development start?
First 6h
50
What happens in stage 2 of in vitro neuronal development?
Neurites are formed
51
What is a neurite?
Small protrusions that are not distinguishable between each other in composition and morphology, and have no function
52
When does stage 2 of in vitro neuronal development start?
After 6h
53
What happens in stage 3 of in vitro neuronal development?
One neurite grows rapidly to form the axon and gain the molecular determinants of the axon
54
What step in in vitro neuronal development is "breaking of the symmetry"?
Stage 3 (axon initiation)
55
What is "breaking of the symmetry"?
The process that begins polarization (stops the cell from being homogeneous)
56
When does stage 3 of in vitro neuronal development start?
After 24h
57
What happens in stage 4 of in vitro neuronal development?
The other neurites become dendrites
58
When does stage 4 of in vitro neuronal development start?
After 2-3 days
59
What happens in stage 5 of in vitro neuronal development?
The dendrites and axon matures
60
When does stage 5 of in vitro neuronal development start?
After 4 days
61
What are the 5 stages of in vitro neuronal development?
1. Random cytoskeletal protrusions
2. Formation of neurites
3. Axon initiation and formation
4. Dendrite formation
5. Axon and dendrite maturity
62
What areas of the brain are most often studied?
The hippocampus and cortex
63
Why are the cortex and hippocampus commonly studied?
They are the major cognitive regions of the brain
64
How does an in vitro study to study neuronal development work?
The neural tissue is dissociated, and the neurons are plated on a petri dish to monitor their development
65
What stage of in vitro neuronal development does random cytoskeletal protrusions occur in?
Stage 1
66
What stage of in vitro neuronal development does neurite formation occur in?
Stage 2
67
What stage of in vitro neuronal development does axon initiation and formation occur in?
Stage 3
68
What stage of in vitro neuronal development does dendrite formation occur in?
Stage 4
69
What stage of in vitro neuronal development does axon and dendrite maturity occur in?
Stage 5
70
What drives neuronal development in vitro?
Intrinsic signaling mechanisms
71
In in vitro neuronal development, what do the "tagged" proteins do before axon initiation?
Jumps randomly around the cell (different neurites)
72
In in vitro neuronal development, what do the "tagged" proteins do after axon initiation?
Localize entirely within the axon
73
How is neuronal development studied in vivo?
Can slice the rodent brain to observe neuronal development
74
True or false: the brain is a highly connected organ
True: there are many neuronal processes that connect together
75
What is the significance of the brain being highly connected?
It makes it difficult to measure neuronal development at the single cell level
76
What is the advantage and challenge of studying neuronal development in vivo?
Want the accuracy and precision of examining single cells developing in a natural environment
77
Where does the primitive brain form from?
A neural tube
78
What does the front of the neural tube turn into?
The structures of the brain
79
What does the back of the neural tube turn into?
The structures of the spinal cord
80
What is the significance of the tissue lining the void space of the neuronal tube?
That is where neuronal cells are generated during embryonic development
81
Where are neuronal cells generated during embryonic development?
On the tissue lining the void space of the neural tube
82
True or false: neuronal development in vitro is the same as in vivo
False: they are slightly different processes
83
What do new neuronal cells do in vivo (first stage)?
Form two neurites
84
What does the "bottom" neurite do in vivo (during development)?
Becomes the axon
85
What does the "top" neurite do in vivo (during development)?
Becomes the different dendrites
86
True or false: neurons in vivo form several neurites
True: however, this is very transient
87
What is a bipolar cell?
A neuron with two processes
88
Where is a bipolar cell seen in neuronal development?
In vivo (two processes which become the axon and dendrites)
89
What is the difference between in vitro and in vivo studies of neuronal development that explains the different processes?
The presence or absence of external cues
90
What are the external cues found in neuronal development in vivo?
BDNF and semaphorin
91
What does semaphorin do?
Promote dendrite formation
92
What does BDNF do?
Promote axon formation
93
In vivo, how can a neuron determine which neurite will become the axon or dendrite?
By the concentrations of extracellular cues (semaphorin and BDNF)
94
True or false: there are equal concentrations of semaphorin and BDNF on either side of the neuron
False: concentration gradients of these extracellular cues leads to neuronal polarization (dendrites vs. axons)
95
How are extracellular cues presented to the neuron?
In gradients of concentration
96
True or false: at the dendrite, there is zero concentration of BDNF
False: there is a low, but nonzero, concentration
97
True or false: at the axon, there is zero concentration of semaphorin
False: there is a low, but nonzero, concentration
98
What concentrations of extracellular cues do dendrites see in vivo?
High concentration of semaphorin, low concentrations of BDNF
99
What concentrations of extracellular cues do axons see in vivo?
High concentration of BDNF, low concentrations of semaphorin
100
What drives neuronal development in vivo?
Activation of intrinsic signaling by extrinsic factors
101
What is the difference in processes between in vivo and in vitro neuronal development?
In vivo, a bipolar cell is formed, while in vitro, many neurites are formed on one cell
102
What do neural cells and epithelial cells have in common?
They are both polarized cells driven by similar molecular principles
103
What domain in neurons is analogous to the apical layer in epithelial cells?
Axon
104
What domain in neurons in analogous to the basolateral layer in epithelial cells?
Dendrites
105
What domain in epithelial cells is analogous to the axon in neurons?
Apical
106
What domain in epithelial cells is analogous to the dendrites in neurons?
Basolateral
107
What is the significance of neurons and epithelial cells having analogous domains?
The signaling determinants that dictate and execute these polarized phenotypes are conserved across different cell types and different species
108
True or false: it is possible to have two genes with different functions to be expressed together (ex: axon and dendrite formation)
True: as long as an upstream activator specifically activates one gene in the correct location
109
True or false: an upstream regulator can rescue a function of a downstream regulator
False: there is nothing downstream to cause the effect
110
True or false: a downstream regulator can rescue a function of an upstream regulator
True: the downstream regulator can still be activated by something else to cause the effect
111
If PKA is important for axon development, what will overexpression of PKA do?
Result in the formation of many axons
112
What protein family is seen in polarization?
The PAR protein family
113
How many PAR proteins are there?
6 (PAR1-PAR6)
114
What does PAR stand for?
Partitioning defective
115
What model system was used to identify the PAR proteins?
C. elegans
116
What was the purpose of the experiments that discovered the PAR proteins?
To find the proteins that mediated the polarized division of the fertilized C. elegans egg
117
What happens to a fertilized C. elegans egg?
It divides into two polarized regions, by sending different cellular components to either side
118
What mediates the polarized division of the fertilized C. elegans egg?
The PAR proteins
119
Before the division, how are PAR3 and PAR6 distributed?
Randomly (symmetrically)
120
What type of protein is PAR1?
A serine/threonine kinase
121
What type of protein is PAR2?
A protein exclusively in C. elegans with a RING domain (ubiquitination)
122
What type of protein is PAR3?
A PDZ domain protein (cellular scaffold)
123
What type of protein is PAR4?
A serine/threonine kinase
124
What type of protein is PAR5?
A member of the 14-3-3 family
125
What type of protein is PAR6?
A PDZ domain protein (cellular scaffold)
126
Which PAR proteins are kinases?
PAR1 and PAR4
127
Which PAR proteins are scaffolds?
PAR3 and PAR6
128
Which PAR proteins will be emphasized in polarization?
PAR1, PAR3, PAR4, and PAR6
129
True or false: the PAR proteins are in the same family since they have similar functions
False: the PAR proteins are all from very different families
130
What are the PAR proteins in a fertilized C. elegans egg an example of?
Polarization through molecular segregation
131
What is the mammalian homolog of PAR4?
LKB1
132
What is LKB1?
A mammalian homolog of PAR4
133
What was the prevailing thought about epithelial cell polarization?
That epithelial cells needed to adhere together to polarize
134
What evidence contradicted the prevailing thought about epithelial cell polarization?
A single polarized epithelial cell (isolated)
135
What protein mediates the polarization of epithelial cells?
LKB1
136
How can you test for a polarized phenotype?
Fluorescently tag a protein, and see how it polarizes (ex: see the microvillae on an epithelial cell's apical domain), or use a knockout / overexpression of a gene
