Axon Guidance 2

Question 1

What does actin growth or retraction depend on?

Answer 1

balance of actin polymerisation and depolymerisation

Question 2

examples of chemoattractive cues

Answer 2

netrins or neurotrophins

Question 3

active/permissive physical cues

Answer 3

ECM or cell adhesion

Question 4

inhibitory or repulsive physical cues

Answer 4

ECM or myelin

Question 5

trophic support

Answer 5

NGF for survival

Question 6

target derived substrate-bound inhibitory gradients

Answer 6

ephrins

Question 7

chemorepulsive cues

Answer 7

MAG or semas

Question 8

Ig superfamily of cell adhesion molecules

Answer 8

CAMs

Question 9

cadherins

Answer 9

cell adhesion molecule

N-cadherin nervous system

Question 10

what links cadherins to cytoskeleton?

Answer 10

catenins

Question 11

what does N-cadherin depend on?

Answer 11

calcium

Question 12

DO cadherins bind homophiliclaly or heterophilically?

Answer 12

homophilically

Question 13

what do ECM molecules bind to?

Answer 13

integrin receptors

Question 14

examples of ECM molecules

Answer 14

laminin
fibronectin
tenascin
proteoglycans - CSPG

Question 15

how many netrin receptors?

Answer 15

4 - DCC, unc5, neogenin and adenosine A2br

Question 16

what netrin receptors for attraction?

Answer 16

DCC multimerisation

Question 17

what netrin receptor for repulsive properties?

Answer 17

cis-binding of unc5

Question 18

how does netrin-DD result in attraction?

Answer 18

activation of RhoGTPases cdc42 and rac

Question 19

A2bR - complex, function

Answer 19

complex with DCC or netrin binds alone
block receptor prevent netrin induced growth cone guidance
activate adenylate cyclase - stimulation of cAMP

Question 20

what to slits tend to do to axons?

Answer 20

repulsion

Question 21

slit/robo mediated repulsion

Answer 21

GAP inactivation of cdc42
antagonism of Ena
silence netrin-DCC

Question 22

what do semaphorins bind to?

Answer 22

neuropilin/plexin complexes

Question 23

what class of semas require neuropilin co-receptor?

Answer 23

3

Question 24

How many semaphorins and families?

Answer 24

over 30, 8 subfamilies

all have conserved sema domain

Question 25

class 4 semas

Answer 25

PAK activated inhibit myosin and cofilin by LIMK growth cone extension Rho A - repulsion

Question 26

how do class 3 semas work

Answer 26

Rho pathway - LIMK activate cofilin and repulsion | can be overriden by blocking LIMK

Question 27

myelin proteins - what are they and their receptors?

Answer 27

Nogo, MAG, OMgp | Nogo receptor and p75 co-receptor

Question 28

NOgoA

Answer 28

NOgo-66 due to 66 aa sequence

Question 29

what ganglioside is involved in mediating MAG effects?

Answer 29

Gt1b

Question 30

what happens following p75 activation by myelin ligands?

Answer 30

rhoA activation | growth cone inhibition

Question 31

guidepost cells - sema2

Answer 31

d/v and distal/proximal gradients initial axon growth to CNS perturbation of sema2 or ROCK - pathfinding errors

Question 32

guidepost cells - sema 1

Answer 32

perturbation = pathfinding errors | axons still travel in correct general direction

Question 33

inhibitory factors expressed by roofplate

Answer 33

BMP, slits, ephrins, semas, proteoglycans

Question 34

what attraction for commissural neurons is expressed at floorplate?

Answer 34

netrins

Question 35

why do axons not cross floor plate again?

Answer 35

robo expression increases due to protein - commissureless in invertebrates not known in humans robo silence netrin-DCC

Question 36

when is axon regeneration across DREZ not possible?

Answer 36

few days after birth | oligodendrocytes, myelin

Question 37

peripheral nerve injury

Answer 37

wallerian degeneration schwann cells and mo cytoskeleton degenerates tube of schwann cells remain

Question 38

astrocytic scar

Answer 38

myelin, proteoglycans, netrin - repulsive in adults axons

Question 39

what happens to cAMP in delvelopment?

Answer 39

downregulated

Question 40

cAMP in embryos

Answer 40

bind Epac - attraction preferentially | bind PKA little repulsion

Question 41

cAMP in adult

Answer 41

bind PKA preferentially | no Epac mediated attraction

Question 42

what happens to neuropilin/plexin receptors in development?

Answer 42

upregulated early embryonic growth cones unaffected by sema3A receptors - collapse