Axonal Guidance 1 Flashcards
describe growth cone
filopodia - F actin finger tips
lamellipodia - actin
MT - interact with filopodia to stabilise them
stable in central region of growth cone
3 regions of growth cone and explain
peripheral - spiky lamellipodia and filopodia
transitional - MT and actin interact
central region - MT stabilise
where is F-actin found in growth cone? what is different in filopodia?
throughout
polarised
what MTs occupy body of growth cone and interact with actin at proximal ends of filopodia?
tyrosinated
what MTs are more stable and in central region not interacting with filopodia?
acetylated
what does MT consolidation depend on?
rate of neurite growth
name 3 things axon guidance requires
neurite initiation
axon growth and pathfinding to target
axon termination and survival in target tissue
what does neurite initiation require?
cytoskeletal rearrangement
before neurite initiation…
actin filaments distributed evenly around MT rich cell body
MT can associate with actin filaments
what forms backbone of neurite?
MT
where do actin filaments localise following neurite outgrowth?
tips
what side of actin filament is ATP actin added ?
barbed distal end
what side of actin filament is ADP actin released?
proximal pointed end
actin tradmilling
ATP actin added at same rate ADP actin released - no increase in filament length
MT - polarised subunits added and removed
alpha/GTP-b tubulin added to plus end
alpha/GDP-b tubulin removed from minus end
examples of post translational tubulin modification and what it does
detyrosination or acetylation
ages and stabilised MT
ADF/cofilin
actin binding proteins which disassemble actin filaments
when is ADF/cofilin deactivated?
phosphorylated by LIM kinase
another function of ADF/cofilin
aids dissociation of ADP-actin
what happens following deactivation of ADF/cofilin?
stabilised in active form by proteins
re-activated by phosphatases
what activates phosphatase slingshot?
AKt1
part of PIP3 receptor activation
what can PIP3 do to result in deactivation of ADF/cofilin?
activate specfic regulators of Rho GTPases to induce LIMK
what activates and deactivates Rho GTpases?
activate = GEfs inactivate = GAPs
does myosin promote retrograde or anterograde flow of actin filament?
retrograde
how do rac and cdc42 promote filopodial elongation?
block MLC phosphatase, block myosin
How does Rho result in retraction?
block MLC phosphatase, stimulate myosin
examples of proteins promoting filamental branching
scar, N-wasp, Arp 2/3
Examples of things that prevent capping of actin filaments
Rac
Ena/VASP family
profilin
What do activated GEFs do?
Rho GDP –> Rho GTP
what do activated GAPs do?
Rho GTP –> Rho GDP
3 stages of filopodial outgrowth
protrusion
engorgement
consolidation of neurite
3 main forms of axon guidance
chemical - chemotropism
electrical eg guidepost cells
physical - cathode
when was chemoattraction first demonstrated?
NGF
what might happen with chemorepulsion?
arrest or branching to avoid
Guidepost cells in grasshopper embryos
axon grow to CNS - intermediate pre-axonogenic neuron keeps it on course to turn to target
physical guidance cues examples
pre-axonogenic neurons
continuous chains of cells eg epithelial cells at boundaries
axon tram lines
what does current flow in embryo depend on?
tissue resistance/tissue thickness
EF detected in embryo
neural folds
blastopore
across neural tube
EF - what do neurons grow towards?
cathode
erk protein EF
oriented cathodally
3 trk signalling mechanisms
signalling endosome
domino
anterograde effector
signalling endosome model
ligand receptor complex internalised by endocytosis
survival signals to nucleus
domino model
ligand binding - ligand dependent propogation of trk phosphorylation back to cell body
retrograde effector model
messenger molecules trasnport to cell body
bind effectors or activate trk receptors in soma
