Slit-2 repels the migration of olfactory ensheathing cells by triggering Ca2+-dependent cofilin activation and RhoA inhibition

Zhi Hui Huang, Ying Wang, Zhi Da Su, Jian Guo Geng, Yi Zhang Chen, Xiao Bing Yuan, Cheng He

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Olfactory ensheathing cells (OECs) migrate from the olfactory epithelium towards the olfactory bulb during development. However, the guidance mechanism for OEC migration remains a mystery. Here we show that migrating OECs expressed the receptor of the repulsive guidance factor Slit-2. A gradient of Slit-2 in front of cultured OECs first caused the collapse of the leading front, then the reversal of cell migration. These Slit-2 effects depended on the Ca2+ release from internal stores through inositol (1,4,5)-triphosphate receptor channels. Interestingly, in response to Slit-2 stimulation, collapse of the leading front required the activation of the F-actin severing protein cofilin in a Ca2+-dependent manner, whereas the subsequent reversal of the soma migration depended on the reversal of RhoA activity across the cell. Finally, the Slit-2-induced repulsion of cell migration was fully mimicked by co-application of inhibitors of F-actin polymerization and RhoA kinase. Our findings revealed Slit-2 as a repulsive guidance factor for OEC migration and an unexpected link between Ca2+ and cofilin signaling during Slit-2-triggered repulsion.

Original languageEnglish (US)
Pages (from-to)186-197
Number of pages12
JournalJournal of Cell Science
Volume124
Issue number2
DOIs
StatePublished - Jan 15 2011

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Keywords

  • Ca
  • Cofilin
  • Migration
  • Olfactory ensheathing cells
  • RhoA
  • Slit-2

ASJC Scopus subject areas

  • Cell Biology

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