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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
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Published on: March 9, 2012

Small GTPase Rin induces neurite outgrowth through Rac/Cdc42 and calmodulin in PC12 cells

Mitsunobu Hoshino1, Shun Nakamura

  • 1Division of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. hoshinom@ncnp.go.jp

The Journal of Cell Biology
|December 10, 2003
PubMed

Insights

The small GTPase Rin promotes neuronal growth by activating Rac/Cdc42 and binding calmodulin (CaM). This Rin-CaM interaction is crucial for calcium-mediated signaling and neurite outgrowth in neurons.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • The Ras-like small GTPase Rin is highly expressed in adult neurons.
  • Rin binds calmodulin (CaM) via its COOH-terminal motif.
  • Rin's role in calcium/CaM-mediated neuronal signaling and its signal transduction pathways remain unclear.

Purpose of the Study:

  • To investigate the role of Rin in neurite outgrowth and its associated signaling pathways.
  • To determine the involvement of Rac/Cdc42 and CaM in Rin-mediated signaling.

Main Methods:

  • Expression of Rin and its mutants in rat pheochromocytoma PC12 cells.
  • Assessing neurite outgrowth.
  • Utilizing dominant-negative Rac/Cdc42 proteins and CaM inhibitors.
  • Measuring endogenous Rac/Cdc42 activity.
  • Disrupting endogenous Rin function.

Main Results:

  • Rin expression induced neurite outgrowth independently of nerve growth factor or MAPK activation.
  • Rin-induced neurite outgrowth was inhibited by dominant-negative Rac/Cdc42 or CaM inhibitors.
  • Rin expression increased endogenous Rac/Cdc42 activity.
  • Rin mutants unable to bind CaM failed to induce neurite outgrowth.
  • Disrupting endogenous Rin inhibited forskolin- and KCl-stimulated neurite outgrowth.

Conclusions:

  • Rin-mediated neurite outgrowth signaling necessitates both Rac/Cdc42 activation and Rin-CaM association.
  • Endogenous Rin plays a role in calcium/CaM-mediated neuronal signaling pathways.
  • Rin is a key mediator in neuronal development and calcium signaling.

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