A critical role for STIM1 in filopodial calcium entry and axon guidance

Sangwoo Shim, James Q. Zheng, Guo Li Ming

Research output: Contribution to journalArticle

Abstract

Background: Stromal interaction molecule 1 (STIM1), a C2+ sensor in the endoplasmic reticulum, regulates store-operated C2+ entry (SOCE) that is essential for C2+ homeostasis in many types of cells. However, if and how STIM1 and SOCE function in nerve growth cones during axon guidance remains to be elucidated. Results: We report that STIM1 and transient receptor potential channel 1 (TRPC1)-dependent SOCE operates in Xenopus spinal growth cones to regulate C2+ signaling and guidance responses. We found that STIM1 works together with TRPC1 to mediate SOCE within growth cones and filopodia. In particular, STIM1/TRPC1-dependent SOCE was found to mediate oscillatory filopodial C2+ transients in the growth cone. Disruption of STIM1 function abolished filopodial C2+ transients and impaired C2+-dependent attractive responses of Xenopus growth cones to netrin-1. Finally, interference with STIM1 function was found to disrupt midline axon guidance of commissural interneurons in the developing Xenopus spinal cord in vivo. Conclusions: Our data demonstrate that STIM1/TRPC1-dependent SOCE plays an essential role in generating spatiotemporal C2+ signals that mediate guidance responses of nerve growth cones.

Original languageEnglish (US)
Article number51
JournalMolecular Brain
Volume6
Issue number1
DOIs
StatePublished - Dec 1 2013

Keywords

  • Axon guidance
  • C oscillation
  • Calcium
  • Calcium homeostasis
  • Filopodial C entry
  • Netrin-1
  • SOCE
  • STIM1
  • TRPC1

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Biology

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