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Mol Brain December 1, 2013; 6 51.

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

Shim S , Zheng JQ , Ming GL .

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.

PubMed ID: 24289807
PMC ID: PMC3907062
Article link: Mol Brain
Grant support: [+]

Species referenced: Xenopus
Genes referenced: actl6a cpa1 lck stim1 trpc1
Antibodies: Neuronal Ab4
Morpholinos: trpc1 MO1

Article Images: [+] show captions
References [+] :
Akiyama, Control of neuronal growth cone navigation by asymmetric inositol 1,4,5-trisphosphate signals. 2009, Pubmed