JIP1 mediates anterograde transport of Rab10 cargos during neuronal polarization

J Neurosci. 2014 Jan 29;34(5):1710-23. doi: 10.1523/JNEUROSCI.4496-13.2014.

Abstract

Axon development and elongation require strictly controlled new membrane addition. Previously, we have shown the involvement of Rab10 in directional membrane insertion of plasmalemmal precursor vesicles (PPVs) during neuronal polarization and axonal growth. However, the mechanism responsible for PPV transportation remains unclear. Here we show that c-Jun N-terminal kinase-interacting protein 1 (JIP1) interacts with GTP-locked active form of Rab10 and directly connects Rab10 to kinesin-1 light chain (KLC). The kinesin-1/JIP1/Rab10 complex is required for anterograde transport of PPVs during axonal growth. Downregulation of JIP1 or KLC or disrupting the formation of this complex reduces anterograde transport of PPVs in developing axons and causes neuronal polarity defect. Furthermore, this complex plays an important role in neocortical neuronal polarization of rats in vivo. Thus, this study has demonstrated a mechanism underlying directional membrane trafficking involved in axon development.

Keywords: Jip1; Rab10; neuronal polarity; vesicle trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Axons / metabolism
  • Brain / cytology
  • Cell Polarity / physiology*
  • Cells, Cultured
  • Cellular Structures / metabolism
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation / physiology
  • Humans
  • Ki-67 Antigen / metabolism
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Microscopy, Confocal
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Neurons / cytology
  • Neurons / physiology*
  • Protein Transport / physiology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • T-Box Domain Proteins / metabolism
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Ki-67 Antigen
  • Luminescent Proteins
  • Mapk8ip1 protein, rat
  • Microtubule-Associated Proteins
  • RNA, Small Interfering
  • Rab10 protein, rat
  • T-Box Domain Proteins
  • kinesin light-chain proteins
  • rab GTP-Binding Proteins