STI1 Antagonizes Cytoskeleton Collapse Mediated by Small GTPase Rnd1 and Regulates Neurite Growth

Exp Cell Res. 2014 May 15;324(1):84-91. doi: 10.1016/j.yexcr.2014.03.017. Epub 2014 Mar 29.

Abstract

Rnd proteins comprise a branch of the Rho family of small GTP-binding proteins, which have been implicated in rearrangements of the actin cytoskeleton and microtubule dynamics. Particularly in the nervous system, Rnd family proteins regulate neurite formation, dendrite development and axonal branching. A secreted form of the co-chaperone Stress-Inducible Protein 1 (STI1) has been described as a prion protein partner that is involved in several processes of the nervous system, such as neurite outgrowth, neuroprotection, astrocyte development, and the self-renewal of neural progenitor cells. We show that cytoplasmic STI1 directly interacts with the GTPase Rnd1. This interaction is specific for the Rnd1 member of the Rnd family. In the COS collapse assay, overexpression of STI1 prevents Rnd1-plexin-A1-mediated cytoskeleton retraction. In PC-12 cells, overexpression of STI1 enhances neurite outgrowth in cellular processes initially established by Rnd1. Therefore, we propose that STI1 participates in Rnd1-induced signal transduction pathways that are involved in the dynamics of the actin cytoskeleton.

Keywords: Hop; Neuritogenesis; Rnd1; STI1.

MeSH terms

  • Animals
  • COS Cells
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cytoskeleton / metabolism*
  • Heat-Shock Proteins / physiology*
  • Mice
  • Microtubules / metabolism
  • Neurites / physiology*
  • PC12 Cells
  • Protein Binding
  • Rats
  • Signal Transduction / physiology
  • rho GTP-Binding Proteins / physiology*

Substances

  • Heat-Shock Proteins
  • Rnd1 protein, rat
  • Stip1 protein, rat
  • rho GTP-Binding Proteins