UNC-33 (CRMP) and ankyrin organize microtubules and localize kinesin to polarize axon-dendrite sorting

Nat Neurosci. 2011 Nov 20;15(1):48-56. doi: 10.1038/nn.2970.

Abstract

The polarized distribution of neuronal proteins to axons and dendrites relies on microtubule-binding proteins such as CRMP, directed motors such as the kinesin UNC-104 (Kif1A) and diffusion barriers such as ankyrin. The causative relationships among these molecules are unknown. We show here that Caenorhabditis elegans CRMP (UNC-33) acts early in neuronal development, together with ankyrin (UNC-44), to organize microtubule asymmetry and axon-dendrite sorting. In unc-33 and unc-44 mutants, axonal proteins were mislocalized to dendrites and vice versa, suggesting bidirectional failures of axon-dendrite identity. unc-44 directed UNC-33 localization to axons, where it was enriched in a region that resembled the axon initial segment. unc-33 and unc-44 were both required to establish the asymmetric dynamics of axonal and dendritic microtubules; in their absence, microtubules were disorganized, the axonal kinesin UNC-104 invaded dendrites, and inappropriate UNC-104 activity randomized axonal protein sorting. We suggest that UNC-44 and UNC-33 direct polarized sorting through their global effects on neuronal microtubule organization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ankyrins / genetics
  • Ankyrins / metabolism*
  • Axons / metabolism*
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Polarity / physiology*
  • Dendrites / metabolism*
  • Kinesin / metabolism*
  • Microtubules / metabolism*
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism*
  • Neurons / metabolism*
  • Protein Transport

Substances

  • Ankyrins
  • Caenorhabditis elegans Proteins
  • Nerve Growth Factors
  • unc-33 protein, C elegans
  • Kinesin