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BMS381 Developmental Neurobiology > L1 - Neuronal Polarity > Flashcards

L1 - Neuronal Polarity Flashcards

1
Q

What does neuronal polarity mean?

A

That the two ends of a neurone are different

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2
Q

Fucntion of the axons

A

Responsible for AP generation

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3
Q

Function of dendrites

A

Collect and integrate the incoming stimuli

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4
Q

3 ways in which axons and dendrites are distinct

A

Structurally
Molecularly
Plama Membrane

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5
Q

How are axons strucutually different from dendrites

A

AXONS - highly polarised MTs

DENDRITES - MT less ordered and have mixed orientations

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6
Q

What molecule would be found in axons not dendrites

A

Tau - microtubule assocaited protein

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7
Q

What molecule would be found in dendrites and not axons

A

MAP2

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8
Q

How is the PM membrane of axons different dendrites

A

AXONS - CAM L1

DENDRITES - GluR1

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9
Q

What is GluR1

A

Subunit of the glutamate receptor

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10
Q

What experiemntal method could be used to determine any barriers that exist in a neurones membrane

A

Using optical tweezer

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11
Q

What were the results of an optical tweezer experiments to test for barriers in a neurones membrane

A

Proteins coated in axon protein cant move into the dendrite

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12
Q

The barrier in a neurone is called the

A

Axon initial segement

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13
Q

What does the AIS maintain

A

Somatodendrtic and axonal domains

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14
Q

Who set up the hippocampal neutrite selection paradigm

A

Dotti et all 1988

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15
Q

Describe the results of Dottis neurite selection paradigm

A

Neuron starts as a spherical cell and then progresses extending spouts before finally selecting the aoxn

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16
Q

What can axon selection be visualised with

How does this work?

A

Kif1-GFP

GFP with Kif1 is a plus end directed kinesin so travels to the + end of the microtubule so can see where the axons are forming

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17
Q

The process of axon selection is ______

A

Stochastic

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18
Q

What does stochastic mean

A

A process that appears to be random but full picture might not be understood

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19
Q

How does axon selection happen

A

All of the neurites are tried and tested before one is selected

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20
Q

What do growth cones and neurites contain?

A

Dynamic MTs that are tyrosinated

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21
Q

What do newly polarised axons contain/

A

Stabilised and acetylated microtubules

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22
Q

What can be used to stabilise artifically a microtubule

A

Taxol

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23
Q

What happens if you cut a newly specified axon?

A

Selection of another neurite to become the axon

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24
Q

What are the roles for positive and negative feedback in axon selection (TWO)

A

A) diffusible inhibitor which prevents axon formation in neurites
B) a limitting component

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25
Q

What happens when Hras expression is forced in neurones

A

Forms a neurone with mutliple axons

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26
Q

Where does Hras accumulate - what does this cause

A

Accumulates in the growth cone as symmetry is broken

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27
Q

What is the effect of using a PI3K inhibitor

A

HRas prevented from accumulating in the growth cones ALSO prevents the induction of multiple axons by HRas overexpression

28
Q

The results obtained through the PI3K inhibitor use shows that …

A

HRas works through PI3 kinase

29
Q

What can be used to activated PI3 kinase

A

iRAP

30
Q

Activation of PI3 kinase causes

A

The activation of HRas

31
Q

HRas and PI3 kinase act in a ……

A

Mutually dependent pathway

32
Q

HRas is depeleted from _____________

This is consistent with the _________________ model

A

Non-axonal regions

Limiting component model

33
Q

What type of molecule is Ras

A

A GTPase

34
Q

What is the effect of activated Ras

A

Activation of PI3 kinase

Phosphorylation of PIP2 –> PIP3

35
Q

What does PIP3 activate what does it inhibit

A

ACTIVATE Akt
ACTIVATE Rac
INHIBITOR GSK-3B

36
Q

What is the effect of GSK3B when it HASNT BEEN PHOSPHORYLATED by PIP3

A

Inhibition of microtubule stabilisation

37
Q

With Activation of Akt and Rac and the inhibition of GSK-3B what is the overall effect

A

Microtubules stabilsing and actin dynamics triggered

Leads to actin elongation

38
Q

What do the par genes establish

A

Asymmetric cell division

39
Q

What is the first role of the Par genes

A

Establish polarity following sperm entry

40
Q

What makes up the Par3 complex

A

CDC42
PAR6
PAR3
PKC-3

41
Q

Where do Par3 complex proteins localise

A

In the nascent growth cone

42
Q

Par6 is member of

A

Par3 complex

43
Q

What antagonises PI3 kinase …. how>

A

PTEN

Phosphatase that acts on PIP3

44
Q

Why is PTEN important in cells

A

To prevent CA of PIP3

45
Q

What is the result of PIP3 inhibition by PTEN

A

Prevention of Par3 accumulation blocks axon formation

46
Q

SAD kinases related to

A

Par1

47
Q

What is the result of a loss of SAD kinase

A

Failure of acetylated (stable) tubulin to predominate over tyrosinated tubulin = no axons are formed

48
Q

What is the result of a loss of LKB1 kinase

A

Failure to make axons

49
Q

Describe the model of LKB1, Par3 complex and SADK in axon specification

A

Normally LKB1 inhibits Par3 complex prevening it inhibiting GSK3B
LKB1 phosphorylation inhibits this inhibition (causing activation of GSK3B) and causes activation of the SAD kinases
SAD kinase activation is required for specification of the axons

50
Q

What phosphorylates LKB1

A

Phosphorylation by PK-A

51
Q

What is the action of the phosphorylated LKB1

A

Activation of SAD kinases

52
Q

What is the action once the SADkinases have been activated

A

MAP stability and axon initiation

53
Q

What is the function of the Par3 complex in axon formation in vivo

A

Par3 and PI3K inhibit the inhibition of axon formation by GSk3B also affeected MAPS

54
Q

What is the result of LKB1 loss in the mouse cortex

A

Loss of axon initiation

55
Q

What are tubulinopathies

A

Diseases where mutations are of tubulin

56
Q

What is milder mental retardation associated with

A

TGFB receptor mutations

57
Q

Where are TGFBs expressed? And what is their role

A

Expressed in the VZ of the developing cortex

Can initiated axons in vitro

58
Q

What are the flavours that semaphorins come in?

A

Membrane bound

Secreted

59
Q

Describe the Sema3A gradient … what does this gradient do?

A

Gradient from basal to apical which attracts dendrites basally it also promotes dendrite formation at the expense of axons

60
Q

What is the mechanism by which Sema3A works

A

Raises levels of IIC cGMP and supresses cAMP

Inhibtion of PK-A so it is blocked from the phosphorylation of LKB1 and GSK3B

61
Q

Manipulation of cAMP and cGMP has ______ effects on axon formation

A

OPPOSITE

62
Q

TGFB activates the

A

Par3 complex

63
Q

Members of the Par3 complex include

A

Par3, Par6, aPKC

64
Q

Appically _____ phosphorylates _____ (member of the _______) to promote _____-

A

TGF-B
Par6
Member of Par3
Axon specification

65
Q

Basally ____ increases _______ and decreases _____ thus ______________by ________________ this prvents activation of __________ which is responsible for _______________

A

Basally Sema3a increases cGMP and decreases cAMP thus preventing phosphorylation of LKB1 by PK-A
Prevnets the activation of SAD kinase which is responsible for axon specification

66
Q

Evidence for polarity inheritance

A

In the retina are early cortex, neurones born from radial glia

67
Q

Evidence against polarity inheritance

A

Later cortex, dividing intermediate progenitors that expand neurone numbers, these lose their polarity during division and it must be re-established

BMS381 Developmental Neurobiology (16 decks)

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