Home NEUR 310 Thursday, February 6, 2014

Thursday, February 6, 2014 CC-BY-NC
Neuronal Polarity

Maintainer: admin

1Neuron Polarity

  • influenced by surroundings
    • laminin: promote branch number and outgrowth
    • CSPGs (Chondroitin sulfate proteoglycans): inhibits laminin effects
    • axons can also detect differences in the environment and grow toward the change of substrate
  • intrinsic factor : affecting cytoskeleton
    • actin: barbed end and pointed end
    • microtubule
      • plus end in growth cone
      • mixed orientations in dendrites
      • transports : kinesin toward plus end and dynein toward minus end

2three phases of polarization

  • first : neurite formation

    • cytokinesis ring from division : has RhoA, Aurora A (kinase for Par3) and other remants
    • clustering of these polarity complex proteins leads to formation of a first neurite
    • Golgi and centrioles move toward the growing neurite afterward
    • Par 3 / 6 become enriched at the ip of the future axon
      • eventually lead to changes in actin skeleton

  • Second: Axon specification

    • RhoA inhibits minor neurites from becoming fast growing
    • removal of RhoA leads to one neurite grow into an axon
    • cutting off an axon would lead to a new axon derived from a neurite

    • using taxol to stabilze microtubule of one neurite would make that neurite intoa axon

      • you can get multiple axons by detabilizing F-actin and stailizing microtubule in multiple neurites

    • signaling

      • PIP2/3 leads to phosphorylation of Akt which promotes microtubule growth.

  • Third: Commitment of axon and dendrites

    • they commit to different developmental paths and architectures
    • dendrites: microtubules of mixed polarity, Golgi outposts
    • axon: have neither

3Growth Cone

  • retrograde actin flow destroys polarity of microtubule -> stall outgrwoth

  • actin destabilization and microtubule stabilization -> neuronal outgrowth

  • regulation of outgrowth : at the level fo microtubule and actin

    • MT-associated proteins like tau, MAP, stabilize microtubules
    • arp2/3 complex : for nucleation

4Classes of neurons

  • classification based on their dendritic architecture
  • we used drosophila to study dendrite morphogenesis
  • transcription factors that regulate dendirte development
    • ex: Lola which regulates nucleation of microtubule
    • Spire, another nucleating factor that allows actin extntion
    • Spineless: also affect branching
    • these factors act different on differetn classes of neurons

4.1Coverage of dendrites

  • Dscam1 is alternatively spliced neuronal receptor

  • this allows tilting of class IV neurons (in drosophila)

  • it allows self-avoidance and avoidance of other neurons by Dscam-1 to ensure that dendrites do not have overlapping branches and coverage

    • neurites of the same neuron express identical Dscam1 which leads to homophilic binding, but that translates into repulsion in the same neuron
    • coupled w integrin-dependent adhesion to ECM, the dendrites are enclosed by epidermis and branches do not contact/ cross over each other.

  • proteocadherins, also act similarly as Dscam1 in mediate dendritie self-avoidance, but in mammals