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

Mol Brain. 2013 Dec 1:6:51. doi: 10.1186/1756-6606-6-51.


Background: Stromal interaction molecule 1 (STIM1), a Ca2+ sensor in the endoplasmic reticulum, regulates store-operated Ca2+ entry (SOCE) that is essential for Ca2+ 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 Ca2+ 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 Ca2+ transients in the growth cone. Disruption of STIM1 function abolished filopodial Ca2+ transients and impaired Ca2+-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 Ca2+ signals that mediate guidance responses of nerve growth cones.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Axons / metabolism*
  • Calcium / metabolism*
  • Calcium Signaling
  • Calcium-Binding Proteins / metabolism*
  • Cloning, Molecular
  • Growth Cones / metabolism
  • Interneurons / metabolism
  • Nerve Growth Factors / metabolism
  • Netrin-1
  • Protein Transport
  • Pseudopodia / metabolism*
  • Spinal Cord / metabolism
  • Stromal Interaction Molecule 1
  • TRPC Cation Channels / metabolism
  • Tumor Suppressor Proteins / metabolism
  • Xenopus / metabolism*
  • Xenopus Proteins / metabolism*


  • Calcium-Binding Proteins
  • Nerve Growth Factors
  • STIM1 protein, Xenopus
  • Stromal Interaction Molecule 1
  • TRPC Cation Channels
  • TRPC1 protein, Xenopus
  • Tumor Suppressor Proteins
  • Xenopus Proteins
  • Netrin-1
  • Calcium