Module 1 Lecture 4: Axon Guidance Flashcards
main characteristic of the growth cone
engine and navigator of axon guidance
what major cytoskeletal systems are essential for dynamics
- microtubules (MTs) (common in cell division - spindle)
- actin (makes up thin filaments in muscles to shorten them)
how are microtubules and actin assembled
from monomers into polymers
what are the two poles of the polymers
fast growing plus and slow growing minus ends
- structurally and kinetically distinct
where does the plus end of the polymer point
toward the leading edge of growth cone
what drives growth cone movement
new polymer assembly
what composes the peripheral domain
- long, bundled actin filaments in filopodia (exploratory structures)
- crosslinked actin networks in veil-like structures between filopodia
- individual, dynamic ‘pioneer’ microtubules which reach along actin bundles
what composes the central domain
- stable, bundled microtubules enter the growth cone from the axon shaft
- organelles, vesicles
- central actin bundles
what is the transition zone in the growth cone composed of
- interface between peripheral domain and central domain
- ‘actin arcs’: contractile actin-myosin structures (similar to muscles); perpendicular to actin bundles of the peripheral domain
treadmilling
internal retrograde flow of actin with no net growth cone movement
how do microtubules contribute to axon guidance
necessary for movement
- no new microtubule polymerization = no forward movement
- dynamic microtubules (pioneers out in peripheral domain) also important for steering
how does actin contribute to axon guidance
necessary for guidance
- growth cone without actin dynamics can move but cannot navigate
- growth cones turn in the direction of net actin assembly
retrograde flow (‘idling engine’)
actin assembled at the leading edge but pulled back at the transition zone by myosin
- no (or little) net movement
what is a clutch
in a car, a mechanical system that connects rotational motion produced by the engine to the wheels
what is the clutch made up of in the growth cone
protein assemblies that physically link the actin cytoskeleton to the substrate
how does the clutch affect growth cone movement
actin assembly pushes the leading edge forward and myosin pulls the rest of the growth cone to follow
- movement! treadmilling stops
what is the adhesive substrate-bound cues (the roadway)
- cell adhesive molecules (CAMs) and cadherins
- extracellular matrix (laminin and fibronectin)
what are the repellent substrate-bound cues (the roadway guard rails)
- slits and ephrins
- chondroitin sulphate proteoglycans
what is the receptor for the substrate-bound, attractive, ECM (laminin and fibronectin)
integrin
integrin receptor function
links extracellular matrix to actin (clutch component)
- growth cones can switch integrin composition through development to alter their responses
what is the receptor for the substrate-bound, repulsive, extracellular matrix (Chondroitin sulphate proteoglycan)
protein tyrosine phosphatase (PTP) sigma
protein tyrosine phosphatase sigma receptor function
Chondroitin sulphate proteoglycan binding to protein tyrosine phosphatase sigma inhibits axon growth through signaling to the actin cytoskeleton
what are the substrate-bound, attractive, cell surface molecules (the surface is another cell, not extracellular matrix)
- cell adhesion molecules (CAMs)
- cadherins
cell adhesion molecules characteristics
- bind other CAMs on other cells
- binding can be with same (homophilic) or different CAM (heterophilic)
- intracellular domain links to cytoskeleton (clutch component)
-eg NCAM, L1-CAM, APCAM
