Axonal Guidance 1

Question 1

describe growth cone

Answer 1

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

Question 2

3 regions of growth cone and explain

Answer 2

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

Question 3

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

Answer 3

throughout

polarised

Question 4

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

Answer 4

tyrosinated

Question 5

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

Answer 5

acetylated

Question 6

what does MT consolidation depend on?

Answer 6

rate of neurite growth

Question 7

name 3 things axon guidance requires

Answer 7

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

Question 8

what does neurite initiation require?

Answer 8

cytoskeletal rearrangement

Question 9

before neurite initiation…

Answer 9

actin filaments distributed evenly around MT rich cell body

MT can associate with actin filaments

Question 10

what forms backbone of neurite?

Answer 10

MT

Question 11

where do actin filaments localise following neurite outgrowth?

Answer 11

tips

Question 12

what side of actin filament is ATP actin added ?

Answer 12

barbed distal end

Question 13

what side of actin filament is ADP actin released?

Answer 13

proximal pointed end

Question 14

actin tradmilling

Answer 14

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

Question 15

MT - polarised subunits added and removed

Answer 15

alpha/GTP-b tubulin added to plus end

alpha/GDP-b tubulin removed from minus end

Question 16

examples of post translational tubulin modification and what it does

Answer 16

detyrosination or acetylation

ages and stabilised MT

Question 17

ADF/cofilin

Answer 17

actin binding proteins which disassemble actin filaments

Question 18

when is ADF/cofilin deactivated?

Answer 18

phosphorylated by LIM kinase

Question 19

another function of ADF/cofilin

Answer 19

aids dissociation of ADP-actin

Question 20

what happens following deactivation of ADF/cofilin?

Answer 20

stabilised in active form by proteins

re-activated by phosphatases

Question 21

what activates phosphatase slingshot?

Answer 21

AKt1

part of PIP3 receptor activation

Question 22

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

Answer 22

activate specfic regulators of Rho GTPases to induce LIMK

Question 23

what activates and deactivates Rho GTpases?

Answer 23

activate = GEfs
inactivate = GAPs

Question 24

does myosin promote retrograde or anterograde flow of actin filament?

Answer 24

retrograde

Question 25

how do rac and cdc42 promote filopodial elongation?

Answer 25

block MLC phosphatase, block myosin

Question 26

How does Rho result in retraction?

Answer 26

block MLC phosphatase, stimulate myosin

Question 27

examples of proteins promoting filamental branching

Answer 27

scar, N-wasp, Arp 2/3

Question 28

Examples of things that prevent capping of actin filaments

Answer 28

Rac Ena/VASP family profilin

Question 29

What do activated GEFs do?

Answer 29

Rho GDP --> Rho GTP

Question 30

what do activated GAPs do?

Answer 30

Rho GTP --> Rho GDP

Question 31

3 stages of filopodial outgrowth

Answer 31

protrusion engorgement consolidation of neurite

Question 32

3 main forms of axon guidance

Answer 32

chemical - chemotropism electrical eg guidepost cells physical - cathode

Question 33

when was chemoattraction first demonstrated?

Answer 33

NGF

Question 34

what might happen with chemorepulsion?

Answer 34

arrest or branching to avoid

Question 35

Guidepost cells in grasshopper embryos

Answer 35

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

Question 36

physical guidance cues examples

Answer 36

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

Question 37

what does current flow in embryo depend on?

Answer 37

tissue resistance/tissue thickness

Question 38

EF detected in embryo

Answer 38

neural folds blastopore across neural tube

Question 39

EF - what do neurons grow towards?

Answer 39

cathode

Question 40

erk protein EF

Answer 40

oriented cathodally

Question 41

3 trk signalling mechanisms

Answer 41

signalling endosome domino anterograde effector

Question 42

signalling endosome model

Answer 42

ligand receptor complex internalised by endocytosis | survival signals to nucleus

Question 43

domino model

Answer 43

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

Question 44

retrograde effector model

Answer 44

messenger molecules trasnport to cell body | bind effectors or activate trk receptors in soma