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

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. © 2013 Shim et al.; licensee BioMed Central Ltd.