title: R-type calcium channels are crucial for semaphorin 3A-induced DRG axon growth cone collapse.
abstract: Semaphorin 3A (Sema3A) is a secreted protein involved in axon path-finding during nervous system development. Calcium signaling plays an important role during axonal growth in response to different guidance cues; however it remains unclear whether this is also the case for Sema3A. In this study we used intracellular calcium imaging to figure out whether Sema3A-induced growth cone collapse is a Ca2+ dependent process. Intracellular Ca2+ imaging results using Fura-2 AM showed Ca2+ increase in E15 mice dorsal root ganglia neurons upon Sema3A treatment. Consequently we analyzed Sema3A effect on growth cones after blocking or modifying intracellular and extracellular Ca2+ channels that are expressed in E15 mouse embryos. Our results demonstrate that Sema3A increased growth cone collapse rate is blocked by the non-selective R- and T- type Ca2+ channel blocker NiCl2 and by the selective R-type Ca2+ channel blocker SNX482. These Ca2+ channel blockers consistently decreased the Sema3A-induced intracellular Ca2+ concentration elevation. Overall, our results demonstrate that Sema3A-induced growth cone collapses are intimately related with increase in intracellular calcium concentration mediated by R-type calcium channels.
authors.affiliation: Biophysical Research Group, Biology department, Vytautas Magnus University, Kaunas, Lithuania; Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Rimantas
authors.initials: R
authors.lastname: Treinys
authors.affiliation: Biophysical Research Group, Biology department, Vytautas Magnus University, Kaunas, Lithuania.
authors.forename: Andrius
authors.initials: A
authors.lastname: Kaselis
authors.affiliation: INCI - UPR-CNRS 3212, Neurotransmission et sécrétion neuroendocrine, Strasbourg, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Jover
authors.affiliation: INSERM U1109, MN3t lab, Labex Medalis, University of Strasbourg, Strasbourg, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bagnard
authors.affiliation: Biophysical Research Group, Biology department, Vytautas Magnus University, Kaunas, Lithuania.
authors.forename: Saulius
authors.initials: S
authors.lastname: Šatkauskas
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020908:Calcium Channels, R-Type / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D005727:Ganglia, Spinal / Q000254:growth & development / Q000378:metabolism*; D020869:Gene Expression Profiling; D020439:Growth Cones / Q000378:metabolism* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009532:Nickel / Q000494:pharmacology; D040121:Semaphorin-3A / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D020908:Calcium Channels, R-Type; D020747:Calcium Channels, T-Type; C108639:SEMA3A protein, human; D040121:Semaphorin-3A; C022838:nickel chloride; D009532:Nickel; D002118:Calcium