Rnd1 regulates axon extension by enhancing the microtubule destabilizing activity of SCG10

J Biol Chem. 2009 Jan 2;284(1):363-71. doi: 10.1074/jbc.M808126200. Epub 2008 Nov 7.

Abstract

The GTPase Rnd1 affects actin dynamics antagonistically to Rho and has been implicated in the regulation of neurite outgrowth, dendrite development, and axon guidance. Here we show that Rnd1 interacts with the microtubule regulator SCG10. This interaction requires a central domain of SCG10 comprising about 40 amino acids located within the N-terminal-half of a putative alpha-helical domain and is independent of phosphorylation at the four identified phosphorylation sites that regulate SCG10 activity. Rnd1 enhances the microtubule destabilizing activity of SCG10 and both proteins colocalize in neurons. Knockdown of Rnd1 or SCG10 by RNAi suppressed axon extension, indicating a critical role for both proteins during neuronal differentiation. Overexpression of Rnd1 in neurons induces the formation of multiple axons. The effect of Rnd1 on axon extension depends on SCG10. These results indicate that SCG10 acts as an effector downstream of Rnd1 to regulate axon extensions by modulating microtubule organization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Differentiation / physiology
  • Cell Line
  • Gene Knockdown Techniques
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microtubule Proteins
  • Microtubules / genetics
  • Microtubules / metabolism*
  • Neurites / metabolism*
  • Protein Structure, Secondary / physiology
  • Protein Structure, Tertiary / physiology
  • Rats
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Microtubule Proteins
  • RND1 protein, human
  • Rnd1 protein, rat
  • STMN2 protein, human
  • Stmn2 protein, rat
  • rho GTP-Binding Proteins