Axon Guidance 2 Flashcards
What does actin growth or retraction depend on?
balance of actin polymerisation and depolymerisation
examples of chemoattractive cues
netrins or neurotrophins
active/permissive physical cues
ECM or cell adhesion
inhibitory or repulsive physical cues
ECM or myelin
trophic support
NGF for survival
target derived substrate-bound inhibitory gradients
ephrins
chemorepulsive cues
MAG or semas
Ig superfamily of cell adhesion molecules
CAMs
cadherins
cell adhesion molecule
N-cadherin nervous system
what links cadherins to cytoskeleton?
catenins
what does N-cadherin depend on?
calcium
DO cadherins bind homophiliclaly or heterophilically?
homophilically
what do ECM molecules bind to?
integrin receptors
examples of ECM molecules
laminin
fibronectin
tenascin
proteoglycans - CSPG
how many netrin receptors?
4 - DCC, unc5, neogenin and adenosine A2br
what netrin receptors for attraction?
DCC multimerisation
what netrin receptor for repulsive properties?
cis-binding of unc5
how does netrin-DD result in attraction?
activation of RhoGTPases cdc42 and rac
A2bR - complex, function
complex with DCC or netrin binds alone
block receptor prevent netrin induced growth cone guidance
activate adenylate cyclase - stimulation of cAMP
what to slits tend to do to axons?
repulsion
slit/robo mediated repulsion
GAP inactivation of cdc42
antagonism of Ena
silence netrin-DCC
what do semaphorins bind to?
neuropilin/plexin complexes
what class of semas require neuropilin co-receptor?
3
How many semaphorins and families?
over 30, 8 subfamilies
all have conserved sema domain
class 4 semas
PAK activated
inhibit myosin and cofilin by LIMK
growth cone extension
Rho A - repulsion
how do class 3 semas work
Rho pathway - LIMK activate cofilin and repulsion
can be overriden by blocking LIMK
myelin proteins - what are they and their receptors?
Nogo, MAG, OMgp
Nogo receptor and p75 co-receptor
NOgoA
NOgo-66 due to 66 aa sequence
what ganglioside is involved in mediating MAG effects?
Gt1b
what happens following p75 activation by myelin ligands?
rhoA activation
growth cone inhibition
guidepost cells - sema2
d/v and distal/proximal gradients
initial axon growth to CNS
perturbation of sema2 or ROCK - pathfinding errors
guidepost cells - sema 1
perturbation = pathfinding errors
axons still travel in correct general direction
inhibitory factors expressed by roofplate
BMP, slits, ephrins, semas, proteoglycans
what attraction for commissural neurons is expressed at floorplate?
netrins
why do axons not cross floor plate again?
robo expression increases due to protein - commissureless in invertebrates not known in humans
robo silence netrin-DCC
when is axon regeneration across DREZ not possible?
few days after birth
oligodendrocytes, myelin
peripheral nerve injury
wallerian degeneration
schwann cells and mo
cytoskeleton degenerates
tube of schwann cells remain
astrocytic scar
myelin, proteoglycans, netrin - repulsive in adults axons
what happens to cAMP in delvelopment?
downregulated
cAMP in embryos
bind Epac - attraction preferentially
bind PKA little repulsion
cAMP in adult
bind PKA preferentially
no Epac mediated attraction
what happens to neuropilin/plexin receptors in development?
upregulated
early embryonic growth cones unaffected by sema3A
receptors - collapse
