Lecture 1 - Neuronal Polarity Flashcards
Why is asymmetry is critical for neuronal function?
The quintessential reason for a neuron’s existence is to mediate intercellular communication.
In neurons this is achieved at the bipartite synapse.
* Signal transmitter — pre-synapse (axon)
* Signal receiver — post-synapse (dendrite)
When does polarity emerge as neurons develop?
Polarity is established between stage 2 and 3 as immature axon forms from neurites
What determines neuronal polarity?
- Selective elongation of a designated neurite initiates axon specification
- This is followed by dendritic specification
- Established via:
1. Cytoskeleton dynamics
2. Polarity signaling pathways
+ intracellular signalling
- How do cytoskeletal dynamics determine neuronal polarity?
Cytoskeletal tracks are polar (directional)
Dynamically polymerising microtubules extend neurites
Growth cones guide elongation (with intermittent retraction)
What is the structure of the growth cone?
Central (C) domain
* Stable bundled MTS
* Numerous organelles, vesicles and central actin bundles
Transition (T) zone
* interface between the P and C domains
* Contains actomyosin contractile structures (actin arcs) perpendicular to F-actin bundles.
* Regulate growth cone shape and movement
Peripheral (P) domain
* long, bundled actin filaments (F-actin bundles) which form the filopodia
* mesh-like branched F-actin networks, which give structure to lamellipodia-like veils.
* dynamic ‘pioneer’ microtubules (MTS)
Growth cone
What is the Central (C) domain?
Central (C) domain
* Stable bundled MTS
* Numerous organelles, vesicles and central actin bundles
Growth cone
What is the Transition (T) zone?
Transition (T) zone
* interface between the P and C domains
* Contains actomyosin contractile structures (actin arcs) perpendicular to F-actin bundles.
* Regulate growth cone shape and movement
Growth cone
What is the Peripheral (P) domain?
Peripheral (P) domain
* long, bundled actin filaments (F-actin bundles) which form the filopodia
* mesh-like branched F-actin networks, which give structure to lamellipodia-like veils.
* dynamic ‘pioneer’ microtubules (MTS)
What are the 4 changes in growth cones in axon outgrowth?
(a) Encounter
i. Binding of growth cone receptors at distal end of the growth cone to adhesive substrate activates intracellular signaling cascades.
ii. Formation of a molecular ‘clutch’ (or grip) that links the substrate to the actin cytoskeleton.
(b) Protrusion
i. During protrusion, this clutch strengthens, prevents backward flow of filamentous (F)-actin.
ii. F-actin polymerization continues in front of the clutch site, the lamellipodia-like veils and filopodia of the peripheral (P) domain move forward to extend the leading edge
(c) During engorgement, F-actin arcs reorientate from the C domain towards the site of new growth. Microtubules in the C domain move towards site of new growth.
(d) Consolidation of the recently advanced C domain occurs as the proximal part of the growth cone compacts at the growth cone neck to form a new segment of axon shaft. The myosin II-containing actin arcs compress the MTS into the newly localized C domain (followed by MT-associated protein stabilization).
Growth cones in axon outgrowth
What happens during (a) Encounter?
(a) Encounter
i. Binding of growth cone receptors at distal end of the growth cone to adhesive substrate activates intracellular signaling cascades.
ii. Formation of a molecular ‘clutch’ (or grip) that links the substrate to the actin cytoskeleton.
Growth cones in axon outgrowth
What happens during (b) Protrusion?
(b) Protrusion
i. During protrusion, this clutch strengthens, prevents backward flow of filamentous (F)-actin.
ii. F-actin polymerization continues in front of the clutch site, the lamellipodia-like veils and filopodia of the peripheral (P) domain move forward to extend the leading edge
Growth cones in axon outgrowth
What happens during (c) Engorgement?
(c) During engorgement, F-actin arcs reorientate from the C domain towards the site of new growth. Microtubules in the C domain move towards site of new growth.
Growth cones in axon outgrowth
What happens during (d) Consolidation?
(d) Consolidation of the recently advanced C domain occurs as the proximal part of the growth cone compacts at the growth cone neck to form a new segment of axon shaft. The myosin II-containing actin arcs compress the MTS into the newly localized C domain (followed by MT-associated protein stabilization).
Why don’t axons (and dendrites) retract?
Microtubule-associated proteins (MAPs) stabilise microtubule tracks
Where do some MAPs exhibit selective localisation?
MAP2 selectively in dendrites
