Axonal Guidance 1 Flashcards

1
Q

describe growth cone

A

filopodia - F actin finger tips
lamellipodia - actin
MT - interact with filopodia to stabilise them
stable in central region of growth cone

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2
Q

3 regions of growth cone and explain

A

peripheral - spiky lamellipodia and filopodia
transitional - MT and actin interact
central region - MT stabilise

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3
Q

where is F-actin found in growth cone? what is different in filopodia?

A

throughout

polarised

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4
Q

what MTs occupy body of growth cone and interact with actin at proximal ends of filopodia?

A

tyrosinated

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5
Q

what MTs are more stable and in central region not interacting with filopodia?

A

acetylated

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6
Q

what does MT consolidation depend on?

A

rate of neurite growth

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7
Q

name 3 things axon guidance requires

A

neurite initiation
axon growth and pathfinding to target
axon termination and survival in target tissue

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8
Q

what does neurite initiation require?

A

cytoskeletal rearrangement

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9
Q

before neurite initiation…

A

actin filaments distributed evenly around MT rich cell body

MT can associate with actin filaments

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10
Q

what forms backbone of neurite?

A

MT

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11
Q

where do actin filaments localise following neurite outgrowth?

A

tips

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12
Q

what side of actin filament is ATP actin added ?

A

barbed distal end

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13
Q

what side of actin filament is ADP actin released?

A

proximal pointed end

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14
Q

actin tradmilling

A

ATP actin added at same rate ADP actin released - no increase in filament length

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15
Q

MT - polarised subunits added and removed

A

alpha/GTP-b tubulin added to plus end

alpha/GDP-b tubulin removed from minus end

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16
Q

examples of post translational tubulin modification and what it does

A

detyrosination or acetylation

ages and stabilised MT

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17
Q

ADF/cofilin

A

actin binding proteins which disassemble actin filaments

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18
Q

when is ADF/cofilin deactivated?

A

phosphorylated by LIM kinase

19
Q

another function of ADF/cofilin

A

aids dissociation of ADP-actin

20
Q

what happens following deactivation of ADF/cofilin?

A

stabilised in active form by proteins

re-activated by phosphatases

21
Q

what activates phosphatase slingshot?

A

AKt1

part of PIP3 receptor activation

22
Q

what can PIP3 do to result in deactivation of ADF/cofilin?

A

activate specfic regulators of Rho GTPases to induce LIMK

23
Q

what activates and deactivates Rho GTpases?

A
activate = GEfs
inactivate = GAPs
24
Q

does myosin promote retrograde or anterograde flow of actin filament?

A

retrograde

25
Q

how do rac and cdc42 promote filopodial elongation?

A

block MLC phosphatase, block myosin

26
Q

How does Rho result in retraction?

A

block MLC phosphatase, stimulate myosin

27
Q

examples of proteins promoting filamental branching

A

scar, N-wasp, Arp 2/3

28
Q

Examples of things that prevent capping of actin filaments

A

Rac
Ena/VASP family
profilin

29
Q

What do activated GEFs do?

A

Rho GDP –> Rho GTP

30
Q

what do activated GAPs do?

A

Rho GTP –> Rho GDP

31
Q

3 stages of filopodial outgrowth

A

protrusion
engorgement
consolidation of neurite

32
Q

3 main forms of axon guidance

A

chemical - chemotropism
electrical eg guidepost cells
physical - cathode

33
Q

when was chemoattraction first demonstrated?

A

NGF

34
Q

what might happen with chemorepulsion?

A

arrest or branching to avoid

35
Q

Guidepost cells in grasshopper embryos

A

axon grow to CNS - intermediate pre-axonogenic neuron keeps it on course to turn to target

36
Q

physical guidance cues examples

A

pre-axonogenic neurons
continuous chains of cells eg epithelial cells at boundaries
axon tram lines

37
Q

what does current flow in embryo depend on?

A

tissue resistance/tissue thickness

38
Q

EF detected in embryo

A

neural folds
blastopore
across neural tube

39
Q

EF - what do neurons grow towards?

A

cathode

40
Q

erk protein EF

A

oriented cathodally

41
Q

3 trk signalling mechanisms

A

signalling endosome
domino
anterograde effector

42
Q

signalling endosome model

A

ligand receptor complex internalised by endocytosis

survival signals to nucleus

43
Q

domino model

A

ligand binding - ligand dependent propogation of trk phosphorylation back to cell body

44
Q

retrograde effector model

A

messenger molecules trasnport to cell body

bind effectors or activate trk receptors in soma