The scaffold protein JIP3 functions as a downstream effector of the small GTPase ARF6 to regulate neurite morphogenesis of cortical neurons

FEBS Lett. 2010 Jul 2;584(13):2801-6. doi: 10.1016/j.febslet.2010.05.020. Epub 2010 May 21.

Abstract

The small GTPase ADP-ribosylation factor 6 (ARF6) plays crucial roles in a wide variety of cell functions. To better understand the molecular mechanisms of ARF6-mediated signaling and cellular functions, we sought new ARF6-binding proteins in the mouse brain. We identified the signaling scaffold protein JNK-interacting protein 3 (JIP3), which is exclusively expressed in neurons, as a downstream effector of ARF6. Overexpression of a unique dominant negative mutant of ARF6, which was unable to interact with JIP3, and knockdown of JIP3 in mouse cortical neurons stimulated the elongation and branching of neurites. These results provide evidence that ARF6/JIP3 signaling regulates neurite morphogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factor 6
  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism*
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Axons / metabolism
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Dendrites / metabolism
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurites / metabolism*
  • Neurogenesis / genetics
  • Neurogenesis / physiology*
  • Neurons / cytology
  • Neurons / metabolism*
  • Protein Binding / genetics
  • Protein Binding / physiology
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • ADP-Ribosylation Factor 6
  • Adaptor Proteins, Signal Transducing
  • Mapk8ip3 protein, mouse
  • Nerve Tissue Proteins
  • Spag9 protein, mouse
  • ADP-Ribosylation Factors
  • ARF6 protein, human
  • Arf6 protein, mouse