Axon Guidance II Flashcards
What are filopodia?
Finger-like projections
What are lamellipodia?
Sheet-like cellular outgrowths
What are filopodia and lamellipodia important for?
Cell shape changes, migrating cells and growth cones
What are the 3 growth cone domains?
- Central (palm)
- Transitional
- Peripheral
What are the 2 filamentous proteins in the growth cone?
1) Microtubules (tubulin)
2) F-actin (filamentous actin)
What is different about the F-actin in filopodia and lamellipodia?
In lamella:
- Actin bundles are crosslinked into a net
In filopodia:
- Actin bundles are polarised to form larger bundles, with a linear array
What is ‘treadmilling’?
- Single actin subunits are added to the tips of the of filaments (F-actin)
- In the peripheral domain, F-actin flows back
- In the transitional domain, the filaments break down into single actin subunits
- In the
Where does treadmilling occur?
In filopodia in a resting growth cone
What happens to the microtubules in the central domain during treadmilling?
They are dragged sporadically dragged into the filopodia
What happens to the movement of the microtubules in the central domain when the growth cone comes into contact with an attractive cue?
The microtubules are more dramatically dragged into the filopodia
What happens in the F-actin when the growth cone comes into contact with an attractive cue?
What does this cause?
- F-actin tread-milling slows down and F-actin accumulates (increases in concentration)
The F-actin accumulation:
- Stabilises the filopodium
- Drags the microtubules into the back of the filopodium - stabilsing the microtubules
When a growth cue is encountered, where do F-actin and microtubules point towards?
How is this done?
Towards the growth cue
Reorganisation of the microtubules to completely establish and new growth direction
When a growth cue is encountered, what 2 key components lead to filopodial extension and reorientation of the microtubules, to point towards the growth cue?
1) MOLECULAR CLUTCH
- Cross-linking to the backwards flowing actin to arrest backwards flow
- Filopodia don’t shorten
- Results in forwards movement of the filopodia (get longer)
2) ACTIN-TUBULIN LINK
- Actin-myosin based link
- Pulls the microtubules into the wake of the extending filopodium
What was discovered when neurons of different types were mixed in culture?
What is this NOT due to?
- Neurons fasciculated only with their OWN kind
- NOT due to attractive forces
What is the ‘growth-cone collapse’?
- F-actin is destabilised
- High to low levels of actin
- Causes the growth cone to retract
When does ‘growth-cone collapse’ occur?
When the growth cone of an axon comes into contact with the axon of another neuron
When ‘growth-cone collapse’ occurs, what happens afterwards?
Growth cone moves in a different direction
What are semaphorins?
- A family of inhibitory guidance cues which can be membrane bound or secretory (have a lipid anchor)
- All have a strongly conserved semaphorin domain
- Non-permissive contact repellants
What happens when add semaphorins to a growth cone?
It moves away, due to dramatic collapse of F-actin (Growth cone collapse)
What does an axon require to allow it to grow?
Must be able to attach to the substrate it is growing on
What is the relationship between strength of adhesion and the amount of axon growth on a substrate?
There is no simple relationship - substrate adhesion does not determine how fast an axon will grow
What are permissive substrates and why are they important?
Substrates which ALLOW growth
Important because attachment alone is not enough for axon growth
Between collagen and laminin, which substance is the most adhesive?
Collagen
Between collagen and laminin, which substance is the most permissive?
Laminin