Neuronal Polarity Flashcards
How does asymmetry exist in cells?
as cell polarity, the non-uniformed distribution of specific molecules and structures
Give examples of where cell polarity is seen
- cytoskeletal components
- intracellular membrane system and lipids
- organelles
- proteins
- mRNA
What is cell polarity important for?
cellular function as it allows cellular activities to be segregated and compartmentalised which in turn allows energetic efficiency
Give examples of polarity in action
- migrating fibroblasts
- cytotoxic T cell
- epithelial cell
- polarised dividing cell
What type of symmetry do neurons exhibit?
morphological and functional
What do the presynaptic and postsynaptic vesicles each have respectively?
- pre = synaptic vesicles (axon)
- post = receptors for these vesicles (dendrite)
What is the main reason for a neurons existence?
to mediate intracellular communication
Where is intracellular communication achieved in neurons?
the bipartite synapse
What happens between stage 2 and 3 of synapse formation?
the immature exon is formed from 1 minor neurite and polarity is initiated; the rest of the neurites become dendrites
What does selective elongation of a designated neurite do?
initiate axon specification which is then followed by dendritic specification
What is dendritic specification established via?
- cytoskeleton dynamics
- polarity signalling molecules
What are the 2 types of cytoskeletal tracks?
short range actin (LRT) and long range MTs (MRT)
What is meant by cytoskeletal tracks being polar?
- plus end points to the outside of the cell
- minus end points to the inside of the cell
What do dendrites show?
reverse polarisation and bidirectionality after stage 4 i.e. ~50% of the tracks become inverted
What do dynamic mitochondria do?
follow wherever cytoskeletal tracks polymerise
What do dynamic polymerising MTs do?
extend neurites
What do growth cones do?
guide neurite elongation i.e. they tell neurons where to go
What are the 3 zones of growth cones?
- central (C) domain
- transition (T) zone
- peripheral (P) domain
What does the C domain contain?
- stable bundles of MTs
- numerous organelles, vesicles and central actin bundles
What is the T zone?
interface between the P and C domains that regulates growth cone shape and movement
What does the T zone contain?
actomyosin contractile structures (actin arcs) perpendicular to F-actin bundles
What is the P domain made up of?
- long, bundled actin filaments (F-actin bundles) that form the filopodia
- mesh-like branched F-actin networks that give structure to lamellipodia-like veils
What must happen for growth cones to move forward?
they must encounter a stimulus (substrate)
What are the 4 steps of growth cones in axon outgrowth?
- encounter
- protrusion
- engorgement
- consolidation
What happens during the encounter stage of axon outgrowth?
- binding of growth cone receptors at distal end of the growth cone to adhesive substrate activates intracellular signalling cascades
- formation of a molecular ‘clutch’ (grip) that links the substrate to the actin cytoskeleton
What happens during the protrusion stage of axon outgrowth?
- the clutch strengthens and prevents backward flow of F-actin
- F-actin polymerisation continues in front of the clutch site, the lamellipodia-like veils and filopodia of the P domain move forward to extend the leading edge
What happens during the engorgement stage of axon outgrowth?
- F-actin arcs reorientate from the C domain towards the site of new growth
- MTs in the C domain move towards the site of new growth
What happens during the consolidation stage of axon outgrowth?
- the proximal part of the growth cone compacts at the growth cone neck to from a new segment of axon shaft
- the myosin II-containing actin arcs compress the MTs into the newly localised C domain (followed by MT-associated protein stabilisation)
How do axons and dendrites not collapse or retract?
MAPs stabilise MT tracks
What are the main MAPs?
MAP-2 and Tau
Where are the 2 MAPs once polarity is established?
- MAP-2 = dendrites
- Tau = axons
What kind of MAP exhibits selective localisation?
Tau protein
What is the negative regulation in stage 2 of axon formation?
- membrane elimination
- degradation of proteins
- decrease in dynamics of F-actin
- MT catastrophe
What is responsible for retraction to extension?
- Rho GTPases and GEF
- PI3K
- centrosome
What is responsible for extension to retraction?
- phosphatase
- Rho GAP
What is the positive regulation in stage 3 of axon formation?
- membrane recruitment
- protein transport
- increase in dynamics of F-actin
- MT assembly
Why does the neuron become an axon at stage 3?
the net congregation of signalling pathways is overwhelmed by positive regulation
What is a prerequisite for axon formation?
MT stabilisation
When does MT stabilisation occur?
when MAPs bind to MTs to prevent them from dissociating regulated by phosphorylation
What does MARK2 do?
destabilise MT tracks
What does PAR-3/PAR-6/atypical PKC complex do?
regulate axon formation through MARK2
What does a reduction in MARK2 do?
decrease the phosphorylation of Tau which stabilises MT tracks to increase the number of mature exons and cause development of multi-axon neurons
What does aPKC lambda in complex with PAR-3/PAR-6 do?
negatively regulate MARK2
Where is aPKCλ + PAR-3 localised?
the presumptive axon
Where are PKM-ζ and PAR-3 localised?
non-axon-forming neurites
What does PKM-ζ do?
compete with aPKC-λ for binding to PAR-3 and disrupt the aPKC-λ–PAR-3 complex
What does silencing of PKM-ζ or overexpression of aPKC-λ in hippocampal neurons do?
alter neuronal polarity, resulting in neurons with supernumerary axons
What does over expression of PKM-ζ do?
prevent axon specification
