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BIO 317 > 10 - Signaling Pathways Directing Cell-Polarization II > Flashcards

10 - Signaling Pathways Directing Cell-Polarization II Flashcards

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1
Q

How is cell polarization characterized?

A

By molecular segregation

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2
Q

How is a functional polarization achieved?

A

By having molecules that perform a specific function segregated in space

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3
Q

What is the purpose of model organisms?

A

Study broad biological principles (such as cell signaling)

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4
Q

What are some examples of model organisms?

A

Drosophila melanogaster (fruit fly), C. elegans (nematoad), zebrafish, and Mus musculus (mouse)

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5
Q

What model organism is the most critical for human?

A

Rodent models

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6
Q

Why are rodent models the most critical for humans?

A

There is a direct implication between rodent and human

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7
Q

What are the advantages of using model organisms?

A

Can be grown easily in the lab, relatively cheap, and easily manipulated

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8
Q

What does “in vitro” mean?

A

In the glass / test tube

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9
Q

What kind of study involves isolated cells in a test tube?

A

In vitro

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10
Q

What are the advantages of an in vitro study?

A

It is easily manipulated and cheaper

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11
Q

What are the disadvantages of an in vitro study?

A

It is a reduced system (does not reflect natural conditions fully)

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12
Q

What does “in vivo” mean?

A

In the living

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13
Q

What kind of study involves doing experiments in the model organism?

A

In vivo

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14
Q

What are the advantages of an in vivo study?

A

The conditions reflect the natural environment

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15
Q

What are the disadvantages of an in vivo study?

A

They are harder to manipulate (not easy or cheap)

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16
Q

What technique is a “combination” of in vivo and in vitro?

A

Ex vivo

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17
Q

What is an ex vivo study?

A

Experiments are done in isolated tissues

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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)

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19
Q

True or false: ex vivo studies perfectly mimic the natural environment

A

False: it only mimics it slightly (based on the tissue)

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20
Q

What cells serve as models for cell polarization?

A

Neurons and epithelial cells

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21
Q

What are epithelial cells?

A

Cells that form tight boundaries (connected sheets)

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22
Q

What do epithelial cells do?

A

Line surfaces and cavities of an organism

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23
Q

What does the function of epithelial cells depend on?

A

The ability to develop and maintain polarized structures

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24
Q

What are the distinct domains of an epithelial cell?

A

Apical and basolateral domains

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25
Q

What separates the apical and basolateral domains?

A

Tight junctions

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26
Q

True or false: the apical domain is morphologically different from the basolateral domain

A

True: the apical domain has microvillae structures, while the basolateral domain does not

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27
Q

What is the structure of the apical domain?

A

Microvillae structures

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28
Q

What are microvillae?

A

Actin protrusions on the apical domain of epithelial cells

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29
Q

What is the function of microvillae?

A

Increase surface area for digestion / absorption

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30
Q

What domain occupies the majority of the epithelial cell?

A

The basolateral domain

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31
Q

True or false: the apical domain is biochemically different from the basolateral domain

A

True: the apical domain and basolateral domain have different cell receptors

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32
Q

How are epithelial cell domains morphologically distinct?

A

The apical domain has microvillae, while the basolateral domain does not

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33
Q

How are epithelial cell domains biochemically distinct?

A

The apical and basolateral domains have different cell surface receptors

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34
Q

What do tight junctions do?

A

Act as a barrier for water and solutes, and restrict movement of cell surface proteins between apical and basolateral domains

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35
Q

What is the significance of tight junctions acting as a barrier for water and solutes?

A

Create distinct extracellular spaces between apical and basolateral domains

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36
Q

What is the significance of tight junctions restricting lateral movement of cell surface proteins?

A

Prevent lateral diffusion to keep the distinct compositions of the apical and basolateral domains

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37
Q

What is needed for proper epithelial cell polarization?

A
  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
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38
Q

What is the most basic building block of brain circuitry?

A

The polarized neuron

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39
Q

What is the name for a cell body for a neuron?

A

The soma

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40
Q

What does the soma contain?

A

Cytoplasm, nucleus, etc.

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41
Q

What are the different compartments of a neuron?

A

The somatodendritic component, and the axon component

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42
Q

What is the morphology of the dendrites?

A

Short, stubby, branched protrusions

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43
Q

What is the morphology of the axon?

A

One long process

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44
Q

What is the function of the axon?

A

To transmit electrical / biochemical neuronal signals

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45
Q

What is the function of the dendrite?

A

Receive and compute signaling information from different axons

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46
Q

How are dendrites and axons (generally) different?

A

In their morphology, molecular composition, and function

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47
Q

What happens in stage 1 of in vitro neuronal development?

A

Cytoskeletal protrusions

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48
Q

What are the characteristics of the cytoskeletal protrusions in stage 1 of in vitro neuronal development?

A

Random and unassigned

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49
Q

When does stage 1 of in vitro neuronal development start?

A

First 6h

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50
Q

What happens in stage 2 of in vitro neuronal development?

A

Neurites are formed

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51
Q

What is a neurite?

A

Small protrusions that are not distinguishable between each other in composition and morphology, and have no function

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52
Q

When does stage 2 of in vitro neuronal development start?

A

After 6h

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53
Q

What happens in stage 3 of in vitro neuronal development?

A

One neurite grows rapidly to form the axon and gain the molecular determinants of the axon

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54
Q

What step in in vitro neuronal development is “breaking of the symmetry”?

A

Stage 3 (axon initiation)

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55
Q

What is “breaking of the symmetry”?

A

The process that begins polarization (stops the cell from being homogeneous)

56
Q

When does stage 3 of in vitro neuronal development start?

A

After 24h

57
Q

What happens in stage 4 of in vitro neuronal development?

A

The other neurites become dendrites

58
Q

When does stage 4 of in vitro neuronal development start?

A

After 2-3 days

59
Q

What happens in stage 5 of in vitro neuronal development?

A

The dendrites and axon matures

60
Q

When does stage 5 of in vitro neuronal development start?

A

After 4 days

61
Q

What are the 5 stages of in vitro neuronal development?

A
  1. Random cytoskeletal protrusions
  2. Formation of neurites
  3. Axon initiation and formation
  4. Dendrite formation
  5. Axon and dendrite maturity
62
Q

What areas of the brain are most often studied?

A

The hippocampus and cortex

63
Q

Why are the cortex and hippocampus commonly studied?

A

They are the major cognitive regions of the brain

64
Q

How does an in vitro study to study neuronal development work?

A

The neural tissue is dissociated, and the neurons are plated on a petri dish to monitor their development

65
Q

What stage of in vitro neuronal development does random cytoskeletal protrusions occur in?

A

Stage 1

66
Q

What stage of in vitro neuronal development does neurite formation occur in?

A

Stage 2

67
Q

What stage of in vitro neuronal development does axon initiation and formation occur in?

A

Stage 3

68
Q

What stage of in vitro neuronal development does dendrite formation occur in?

A

Stage 4

69
Q

What stage of in vitro neuronal development does axon and dendrite maturity occur in?

A

Stage 5

70
Q

What drives neuronal development in vitro?

A

Intrinsic signaling mechanisms

71
Q

In in vitro neuronal development, what do the “tagged” proteins do before axon initiation?

A

Jumps randomly around the cell (different neurites)

72
Q

In in vitro neuronal development, what do the “tagged” proteins do after axon initiation?

A

Localize entirely within the axon

73
Q

How is neuronal development studied in vivo?

A

Can slice the rodent brain to observe neuronal development

74
Q

True or false: the brain is a highly connected organ

A

True: there are many neuronal processes that connect together

75
Q

What is the significance of the brain being highly connected?

A

It makes it difficult to measure neuronal development at the single cell level

76
Q

What is the advantage and challenge of studying neuronal development in vivo?

A

Want the accuracy and precision of examining single cells developing in a natural environment

77
Q

Where does the primitive brain form from?

A

A neural tube

78
Q

What does the front of the neural tube turn into?

A

The structures of the brain

79
Q

What does the back of the neural tube turn into?

A

The structures of the spinal cord

80
Q

What is the significance of the tissue lining the void space of the neuronal tube?

A

That is where neuronal cells are generated during embryonic development

81
Q

Where are neuronal cells generated during embryonic development?

A

On the tissue lining the void space of the neural tube

82
Q

True or false: neuronal development in vitro is the same as in vivo

A

False: they are slightly different processes

83
Q

What do new neuronal cells do in vivo (first stage)?

A

Form two neurites

84
Q

What does the “bottom” neurite do in vivo (during development)?

A

Becomes the axon

85
Q

What does the “top” neurite do in vivo (during development)?

A

Becomes the different dendrites

86
Q

True or false: neurons in vivo form several neurites

A

True: however, this is very transient

87
Q

What is a bipolar cell?

A

A neuron with two processes

88
Q

Where is a bipolar cell seen in neuronal development?

A

In vivo (two processes which become the axon and dendrites)

89
Q

What is the difference between in vitro and in vivo studies of neuronal development that explains the different processes?

A

The presence or absence of external cues

90
Q

What are the external cues found in neuronal development in vivo?

A

BDNF and semaphorin

91
Q

What does semaphorin do?

A

Promote dendrite formation

92
Q

What does BDNF do?

A

Promote axon formation

93
Q

In vivo, how can a neuron determine which neurite will become the axon or dendrite?

A

By the concentrations of extracellular cues (semaphorin and BDNF)

94
Q

True or false: there are equal concentrations of semaphorin and BDNF on either side of the neuron

A

False: concentration gradients of these extracellular cues leads to neuronal polarization (dendrites vs. axons)

95
Q

How are extracellular cues presented to the neuron?

A

In gradients of concentration

96
Q

True or false: at the dendrite, there is zero concentration of BDNF

A

False: there is a low, but nonzero, concentration

97
Q

True or false: at the axon, there is zero concentration of semaphorin

A

False: there is a low, but nonzero, concentration

98
Q

What concentrations of extracellular cues do dendrites see in vivo?

A

High concentration of semaphorin, low concentrations of BDNF

99
Q

What concentrations of extracellular cues do axons see in vivo?

A

High concentration of BDNF, low concentrations of semaphorin

100
Q

What drives neuronal development in vivo?

A

Activation of intrinsic signaling by extrinsic factors

101
Q

What is the difference in processes between in vivo and in vitro neuronal development?

A

In vivo, a bipolar cell is formed, while in vitro, many neurites are formed on one cell

102
Q

What do neural cells and epithelial cells have in common?

A

They are both polarized cells driven by similar molecular principles

103
Q

What domain in neurons is analogous to the apical layer in epithelial cells?

A

Axon

104
Q

What domain in neurons in analogous to the basolateral layer in epithelial cells?

A

Dendrites

105
Q

What domain in epithelial cells is analogous to the axon in neurons?

A

Apical

106
Q

What domain in epithelial cells is analogous to the dendrites in neurons?

A

Basolateral

107
Q

What is the significance of neurons and epithelial cells having analogous domains?

A

The signaling determinants that dictate and execute these polarized phenotypes are conserved across different cell types and different species

108
Q

True or false: it is possible to have two genes with different functions to be expressed together (ex: axon and dendrite formation)

A

True: as long as an upstream activator specifically activates one gene in the correct location

109
Q

True or false: an upstream regulator can rescue a function of a downstream regulator

A

False: there is nothing downstream to cause the effect

110
Q

True or false: a downstream regulator can rescue a function of an upstream regulator

A

True: the downstream regulator can still be activated by something else to cause the effect

111
Q

If PKA is important for axon development, what will overexpression of PKA do?

A

Result in the formation of many axons

112
Q

What protein family is seen in polarization?

A

The PAR protein family

113
Q

How many PAR proteins are there?

A

6 (PAR1-PAR6)

114
Q

What does PAR stand for?

A

Partitioning defective

115
Q

What model system was used to identify the PAR proteins?

A

C. elegans

116
Q

What was the purpose of the experiments that discovered the PAR proteins?

A

To find the proteins that mediated the polarized division of the fertilized C. elegans egg

117
Q

What happens to a fertilized C. elegans egg?

A

It divides into two polarized regions, by sending different cellular components to either side

118
Q

What mediates the polarized division of the fertilized C. elegans egg?

A

The PAR proteins

119
Q

Before the division, how are PAR3 and PAR6 distributed?

A

Randomly (symmetrically)

120
Q

What type of protein is PAR1?

A

A serine/threonine kinase

121
Q

What type of protein is PAR2?

A

A protein exclusively in C. elegans with a RING domain (ubiquitination)

122
Q

What type of protein is PAR3?

A

A PDZ domain protein (cellular scaffold)

123
Q

What type of protein is PAR4?

A

A serine/threonine kinase

124
Q

What type of protein is PAR5?

A

A member of the 14-3-3 family

125
Q

What type of protein is PAR6?

A

A PDZ domain protein (cellular scaffold)

126
Q

Which PAR proteins are kinases?

A

PAR1 and PAR4

127
Q

Which PAR proteins are scaffolds?

A

PAR3 and PAR6

128
Q

Which PAR proteins will be emphasized in polarization?

A

PAR1, PAR3, PAR4, and PAR6

129
Q

True or false: the PAR proteins are in the same family since they have similar functions

A

False: the PAR proteins are all from very different families

130
Q

What are the PAR proteins in a fertilized C. elegans egg an example of?

A

Polarization through molecular segregation

131
Q

What is the mammalian homolog of PAR4?

A

LKB1

132
Q

What is LKB1?

A

A mammalian homolog of PAR4

133
Q

What was the prevailing thought about epithelial cell polarization?

A

That epithelial cells needed to adhere together to polarize

134
Q

What evidence contradicted the prevailing thought about epithelial cell polarization?

A

A single polarized epithelial cell (isolated)

135
Q

What protein mediates the polarization of epithelial cells?

A

LKB1

136
Q

How can you test for a polarized phenotype?

A

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

BIO 317 (27 decks)

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