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

作者：Shim Sangwoo; Zheng James Q^*; Ming Guo li

来源：Molecular Brain, 2013, 6(1): 51.

DOI：10.1186/1756-6606-6-51

• Axon guidance
• STIM1
• SOCE
• TRPC1
• Calcium
• Netrin-1
• Filopodial Ca2+ entry
• Ca2+ oscillation
• Calcium homeostasis

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.

• 出版日期2013-12-1