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BIO 317 > 18 - Adaptation in Axon Pathfinding > Flashcards

18 - Adaptation in Axon Pathfinding Flashcards

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1
Q

What is the gradient of Sema3A?

A

High at the dendrites, low at the axons

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2
Q

How does Sema3A get into the cortex to be detected by the neurons?

A

It is secreted by cells

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3
Q

In terms of Sema3A, where do axons grow?

A

At lower concentrations of Sema3A (repellant)

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4
Q

True or false: the importance of BDNF gradients has been confirmed

A

False: it has not been confirmed genetically

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5
Q

True or false: the importance of Sema3A gradients has been confirmed

A

True: it is known to play an important role in axon growth

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6
Q

If a petri dish has stripes of BDNF, where will the dendrites and axon be?

A

The dendrites will be away from the stripes, and the axon will be on the stripes

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7
Q

If a petri dish has stripes of Sema3A, where will the dendrites and axons be?

A

The dendrites will be on the stripes, and the axon will be away from the stripes

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8
Q

Why is a gradient of extracellular cues important?

A

There would be no reason to grow towards / away something (guided by concentration of factors)

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9
Q

What would happen if there was a constant concentration of extracellular cues?

A

There would not be proper growth, since the cells would not be guided on where to go (based on gradients)

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10
Q

What happens if Sema3A is overexpressed in cortical neurons?

A

The gradient will be abolished, which will impact neuron growth

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11
Q

How can a molecule gradient be abolished?

A

Overexpression or deletion of the molecule

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12
Q

What conclusion can be drawn from the fact that axon initiation starts polarization, and that there is only one axon?

A

The axon must send signals to inhibit the other neurites from becoming an axon

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13
Q

What molecule acts as a negative crosstalk in cell polarization?

A

cGMP

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14
Q

What is needed for the initial breaking of the symmetry?

A

A neurite achieves a threshold of signaling that leads to axon formation

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15
Q

What does the axon do to other neurties?

A

It sends negative signals to prevent them from reaching the threshold signaling to become an axon

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16
Q

What happens in neurites inhibited by the axon?

A

They undergo other signaling to become dendrites (prevent threshold signaling of becoming an axon)

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17
Q

True or false: one neurite can communicate with other neurites

A

True: this leads to only one axon being generated

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18
Q

What happens if cAMP is locally elevated in one neurite?

A

It is locally decreased in other neurites

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19
Q

What drives axon and dendrite formation?

A

Separate signaling pathways that engage in negative communication

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20
Q

Which molecules have opposing roles in regulating axon and dendrite formation?

A

cAMP and cGMP

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21
Q

What properties does cGMP have?

A

Water soluble (intracellular)

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22
Q

What does GC do?

A

Create cGMP from GTP

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23
Q

What enzyme creates cGMP?

A

Guanylyl cyclase (GC)

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24
Q

What enzyme breaks down cGMP?

A

A phosphodiesterase (PDE)

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25
Q

Where are ACs found?

A

In the membrane (transmembrane)

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26
Q

Where are GCs found?

A

In the membrane (transmembrane), or soluble (in the cytoplasm)

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27
Q

What regulates AC?

A

G-proteins

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28
Q

What regulates GC?

A

NO (nitric oxide)

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29
Q

What does NO stand for?

A

Nitric oxide

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30
Q

What is the major source of cGMP in the brain?

A

Soluble GC (sGC)

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31
Q

What does sGC stand for?

A

Soluble guanylyl cyclase

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32
Q

What are the possible downstream targets of cGMP?

A

PKG, ion channels, and cGMP-PDEs

33
Q

What does PKG stand for?

A

Protein kinase G

34
Q

What cellular events use cGMP?

A

Neuronal development, vascular smooth muscle relaxation, and vision

35
Q

True or false: cAMP and cGMP need to be modified to cross the cell membrane

A

True: they are highly water soluble, not lipid soluble

36
Q

True or false: NO needs to be modified to cross the cell membrane

A

False: it is uncharged and nonpolar, so it can easily pass through the cell membrane

37
Q

What are the characteristics of NO?

A

Small, uncharged, and nonpolar

38
Q

What enzyme produces NO?

A

NOS (nitric oxide synthase)

39
Q

What does NOS stand for?

A

Nitric oxide synthase

40
Q

What does NOS do?

A

Converts L-arginine into NO

41
Q

What is nNOS?

A

A neural specific NOS

42
Q

How stable is NO?

A

Very unstable (only active for a few seconds)

43
Q

What is the consequence of NO being highly unstable?

A

It is highly transient and leads to local effects

44
Q

What type of signaling would be ideal for NO?

A

Transient paracrine and autocrine signaling

45
Q

What is the downstream target of NO?

A

sGC

46
Q

What is the structure of sGC?

A

A heterodimer with a beta regulatory domain, and an alpha domain

47
Q

What is the structure of the regulatory domain of sGC?

A

A heme functional group (iron)

48
Q

What is the function of iron in sGC?

A

It acts as a high affinity binding site for NO

49
Q

What happens if no NO is bound to the regulatory domain of sGC?

A

It is inactivated (no cGMP is produced)

50
Q

True or false: NO can only bind to sGC at the iron

A

False: it has two modes of binding (high affinity and low affinity)

51
Q

When does NO bind to the high affinity binding site?

A

At low concentrations

52
Q

When does NO bind to the low affinity binding site?

A

At high concentrations

53
Q

Where is the high affinity binding site?

A

At the heme group

54
Q

What is the activity of sGC at low concentrations of NO?

A

Partial activation (only high affinity binding)

55
Q

What is the activity of sGC at high concentrations of NP?

A

Full activation (low affinity binding too)

56
Q

Why is sGC partially activated at low concentrations of NO?

A

Only binding at the high affinity binding site

57
Q

Why is sGC fully activated at high concentrations of NO?

A

There is also binding at the low affinity binding site

58
Q

What happens if cAMP is presented to a neuron?

A

The axon will grow in the cAMP, and the dendrites will grow outside of the cAMP

59
Q

What happens if cGMP is presented to a neuron?

A

The axon will grow outside of the cGMP, and the dendrites will grow in the cGMP

60
Q

How can the cAMP and cGMP pathway be arranged to antagonize each other?

A
  1. They have opposite actions on common downstream targets

2. Reciprocal regulation (through activation of PDEs)

61
Q

What molecule increases cGMP levels?

A

Sema3A

62
Q

What is the effect of LKB1 when forskolin and Sema3A are added?

A

Decreased phosphorylation

63
Q

Why is there decreased phosphorylation of LKB1 when forskolin and Sema3A are added?

A

The cGMP inhibits the cAMP pathway

64
Q

What is downstream of PKG?

A

Dendrite formation

65
Q

What are the levels of cyclic nucleotides in the axon?

A

High cAMP and low cGMP

66
Q

What are the levels of cyclic nucleotides in the dendrite?

A

High cGMP and low cAMP

67
Q

What happens if PKA is inhibited in a neurite?

A

It will most likely differentiate into an axon

68
Q

True or false: inhibiting PKA has the same phenotype as overexpressing cGMP

A

True: both lead to dendrite formation

69
Q

What determines whether a neurite will be an axon or a dendrite?

A

The relative ratio of determinants from the cAMP and cGMP pathway

70
Q

What is the significance of sGC having two modes of activation?

A

This creates a basal level of cGMP, which can be used in signaling

71
Q

True or false: biological processes are usually at zero

A

False: they usually have a low, basal condition

72
Q

What determines the attraction and repulsion of the axon in axonal pathfinding?

A

The cAMP/cGMP ratio

73
Q

When the cAMP/cGMP ratio is high, what is the phenotype of the axon?

A

Attraction (turn towards it)

74
Q

When the cAMP/cGMP ratio is low, what is the phenotype of the axon?

A

Repulsion (turns away from it)

75
Q

How do guidance cues mediate axon pathfinding?

A

They regulate the cAMP/cGMP ratio

76
Q

What does a positive cue do to the neuron (intracellularly)?

A

Increases the levels of cAMP

77
Q

What does a negative cue do to the neuron (intracellularly)?

A

Increases the levels of cGMP

78
Q

What happens if PKA is inhibited and netrin is presented to the axon?

A

It will shift away from netrin

BIO 317 (27 decks)

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