title: A critical role for STIM1 in filopodial calcium entry and axon guidance.
abstract: 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.
authors.forename: Sangwoo
authors.initials: S
authors.lastname: Shim
authors.affiliation: Departments of Cell Biology and Neurology, Emory University School of Medicine, Atlanta, GA 30078, USA. james.zheng@emory.edu.
authors.forename: James Q
authors.initials: JQ
authors.lastname: Zheng
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Ming
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D020439:Growth Cones / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D000075388:Netrin-1; D021381:Protein Transport; D011554:Pseudopodia / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D014981:Xenopus / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D009414:Nerve Growth Factors; C000589453:STIM1 protein, Xenopus; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels; C502469:TRPC1 protein, Xenopus; D025521:Tumor Suppressor Proteins; D029867:Xenopus Proteins; D000075388:Netrin-1; D002118:Calcium