Tactics and Strategies of Axon guidance Flashcards
What are the 4 tactics of axon guidance?
Haptotaxic - Contact attraction
- Contact repulsion
Chemotaxic - Chemoattraction
- Chemorepulsion
How far can netrin diffuse?
normally expressed in floor plate
may diffuse as far as 0.5mm (half the size of spinal chord at that time)
How to measure gradients?
Temporal detection - change in conc/time
cell must compare amount of ligand at diff time points
Spatial detection - Change in concentration across the cell
What does accuracy of orientation depend on?
- Absolute concentration of chemoattractant
(most accurate response closest to Kd (dissociation constant) of the receptor) - steepness of the gradient
What is the suggested mechanisms for amplification?
clustering of receptor/ signalling components in regions where receptors are activated
- transport components from other parts of the cell
What are chemoattractants detected by?
GPCRs
- activate PI3K
- which phosphorylated PIP2 into PIP3
provide docking sites for proteins containing pleckstrin homology domains
- creates a localised signalling domain on the membrane
What is PI3K antagonised by?
PTEN phosphatase
What do PI3K inhibitors do?
disrupt growth cone turning
The frog axon turning assay showed….. at the growth cone
alternative attractive and repulsive turning
- this suggests cycles of desensitization and sensitisation of the growth cone to netrin
pretreatment of axons to netrin led to
no growth cone response to netrin
What is an example of axon reprogramming?
sensitivity of axons to the floor plate (netrins) changes after the midline is crossed
(in the hindbrain)
What are the inhibitory molecules present in the ventral spinal cord?
semaphorins and slits
What happens when axons cross the floor plate?
Their sensitivities switch
become insensitive to netrin but sensitive to inhibitors
What are slits?
Slits are large secreted proteins shown to act in axon guidance
prohibit growth cone advance an acts as guard rails
What are semaphorins?
diverse family of cel surface and cytosolic proteins
potent activity in promoting growth cone collapse
What are the receptors for semaphorins?
plexins ad neuropilins
What is Robo?
Roundabout (Robo) encodes the membrane receptor for the midline repellant slit
what is the robo mutant?
robo mutant has no longitudinals
the axon crosses the midline glial cells over and over
What is commissureless?
encodes a trafficking protein that prevents robo from reaching the cell surface
What are the comm mutants?
no commissures
everything goes longitudinally
What is the vertebrate homologue of Comm?
PRRG1
how does cell surface expression change after crossing the midline in vertebrates?
TAG-1 -> L1
what does slit induce?
robo trafficking to axons
What occurs in axons before the midline?
PRPG4/ Comm prevents Robo from cycling to the axon
netrin can bind to its receptor DCC
