Neuronal Polarity Flashcards

(48 cards)

1
Q

How does asymmetry exist in cells?

A

as cell polarity, the non-uniformed distribution of specific molecules and structures

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2
Q

Give examples of where cell polarity is seen

A
  • cytoskeletal components
  • intracellular membrane system and lipids
  • organelles
  • proteins
  • mRNA
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3
Q

What is cell polarity important for?

A

cellular function as it allows cellular activities to be segregated and compartmentalised which in turn allows energetic efficiency

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4
Q

Give examples of polarity in action

A
  • migrating fibroblasts
  • cytotoxic T cell
  • epithelial cell
  • polarised dividing cell
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5
Q

What type of symmetry do neurons exhibit?

A

morphological and functional

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6
Q

What do the presynaptic and postsynaptic vesicles each have respectively?

A
  • pre = synaptic vesicles (axon)
  • post = receptors for these vesicles (dendrite)
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7
Q

What is the main reason for a neurons existence?

A

to mediate intracellular communication

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8
Q

Where is intracellular communication achieved in neurons?

A

the bipartite synapse

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9
Q

What happens between stage 2 and 3 of synapse formation?

A

the immature exon is formed from 1 minor neurite and polarity is initiated; the rest of the neurites become dendrites

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10
Q

What does selective elongation of a designated neurite do?

A

initiate axon specification which is then followed by dendritic specification

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11
Q

What is dendritic specification established via?

A
  • cytoskeleton dynamics
  • polarity signalling molecules
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12
Q

What are the 2 types of cytoskeletal tracks?

A

short range actin (LRT) and long range MTs (MRT)

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13
Q

What is meant by cytoskeletal tracks being polar?

A
  • plus end points to the outside of the cell
  • minus end points to the inside of the cell
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14
Q

What do dendrites show?

A

reverse polarisation and bidirectionality after stage 4 i.e. ~50% of the tracks become inverted

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15
Q

What do dynamic mitochondria do?

A

follow wherever cytoskeletal tracks polymerise

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16
Q

What do dynamic polymerising MTs do?

A

extend neurites

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17
Q

What do growth cones do?

A

guide neurite elongation i.e. they tell neurons where to go

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18
Q

What are the 3 zones of growth cones?

A
  • central (C) domain
  • transition (T) zone
  • peripheral (P) domain
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19
Q

What does the C domain contain?

A
  • stable bundles of MTs
  • numerous organelles, vesicles and central actin bundles
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20
Q

What is the T zone?

A

interface between the P and C domains that regulates growth cone shape and movement

21
Q

What does the T zone contain?

A

actomyosin contractile structures (actin arcs) perpendicular to F-actin bundles

22
Q

What is the P domain made up of?

A
  • long, bundled actin filaments (F-actin bundles) that form the filopodia
  • mesh-like branched F-actin networks that give structure to lamellipodia-like veils
23
Q

What must happen for growth cones to move forward?

A

they must encounter a stimulus (substrate)

24
Q

What are the 4 steps of growth cones in axon outgrowth?

A
  1. encounter
  2. protrusion
  3. engorgement
  4. consolidation
25
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
26
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
27
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
28
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)
29
How do axons and dendrites not collapse or retract?
MAPs stabilise MT tracks
30
What are the main MAPs?
MAP-2 and Tau
31
Where are the 2 MAPs once polarity is established?
- MAP-2 = dendrites - Tau = axons
32
What kind of MAP exhibits selective localisation?
Tau protein
33
What is the negative regulation in stage 2 of axon formation?
- membrane elimination - degradation of proteins - decrease in dynamics of F-actin - MT catastrophe
34
What is responsible for retraction to extension?
- Rho GTPases and GEF - PI3K - centrosome
35
What is responsible for extension to retraction?
- phosphatase - Rho GAP
36
What is the positive regulation in stage 3 of axon formation?
- membrane recruitment - protein transport - increase in dynamics of F-actin - MT assembly
37
Why does the neuron become an axon at stage 3?
the net congregation of signalling pathways is overwhelmed by positive regulation
38
What is a prerequisite for axon formation?
MT stabilisation
39
When does MT stabilisation occur?
when MAPs bind to MTs to prevent them from dissociating regulated by phosphorylation
40
What does MARK2 do?
destabilise MT tracks
41
What does PAR-3/PAR-6/atypical PKC complex do?
regulate axon formation through MARK2
42
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
43
What does aPKC lambda in complex with PAR-3/PAR-6 do?
negatively regulate MARK2
44
Where is aPKCλ + PAR-3 localised?
the presumptive axon
45
Where are PKM-ζ and PAR-3 localised?
non-axon-forming neurites
46
What does PKM-ζ do?
compete with aPKC-λ for binding to PAR-3 and disrupt the aPKC-λ–PAR-3 complex
47
What does silencing of PKM-ζ or overexpression of aPKC-λ in hippocampal neurons do?
alter neuronal polarity, resulting in neurons with supernumerary axons
48
What does over expression of PKM-ζ do?
prevent axon specification