Role of the PAR-3-KIF3 complex in the establishment of neuronal polarity

Nat Cell Biol. 2004 Apr;6(4):328-34. doi: 10.1038/ncb1118. Epub 2004 Mar 28.

Abstract

Neurons polarize to form elaborate multiple dendrites and one long axon. The establishment and maintenance of axon/dendrite polarity are fundamentally important for neurons. Recent studies have demonstrated that the polarity complex PAR-3-PAR-6-atypical protein kinase C (aPKC) is involved in polarity determination in many tissues and cells. The function of the PAR-3-PAR-6-aPKC protein complex depends on its subcellular localization in polarized cells. PAR-3 accumulates at the tip of growing axons in cultured rat hippocampal neurons, but the molecular mechanism of this localization remains unknown. Here we identify a direct interaction between PAR-3 and KIF3A, a plus-end-directed microtubule motor protein, and show that aPKC can associate with KIF3A through its interaction with PAR-3. The expression of dominant-negative PAR-3 and KIF3A fragments that disrupt PAR-3-KIF3A binding inhibited the accumulation of PAR-3 and aPKC at the tip of the neurites and abolished neuronal polarity. These results suggest that PAR-3 is transported to the distal tip of the axon by KIF3A and that the proper localization of PAR-3 is required to establish neuronal polarity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axonal Transport / physiology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Differentiation / genetics
  • Cell Polarity / genetics*
  • Cells, Cultured
  • Chlorocebus aethiops
  • Fetus
  • Growth Cones / metabolism
  • Growth Cones / ultrastructure
  • Humans
  • Kinesin / genetics
  • Kinesin / metabolism*
  • Macromolecular Substances
  • Molecular Motor Proteins / metabolism
  • Nerve Tissue Proteins
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Protein Kinase C / metabolism
  • Protein Structure, Tertiary / genetics
  • Protein Transport / genetics*
  • Rats

Substances

  • Carrier Proteins
  • KIF3A protein, human
  • Kif3a protein, rat
  • Macromolecular Substances
  • Molecular Motor Proteins
  • Nerve Tissue Proteins
  • Pard3 protein, rat
  • PKC-3 protein
  • Protein Kinase C
  • Kinesin