title: TRPM7 Regulates Axonal Outgrowth and Maturation of Primary Hippocampal Neurons.
abstract: Transient receptor potential melastatin 7 (TRPM7) is a calcium-permeable divalent cation channel and mediates neuronal cell death under ischemic stresses. In this study, we investigated the contribution of TRPM7 to neuronal development in mouse primary hippocampal neurons. We demonstrated that TRPM7 channels are highly expressed in the tips of the growth cone. Either knockdown of TRPM7 with target-specific shRNA or blocking channel conductance by a specific blocker waixenicin A enhanced axonal outgrowth in culture. Blocking TRPM7 activity by waixenicin A reduced calcium influx and accelerated the polarization of the hippocampal neurons as characterized by the development of distinct axons and dendrites. Furthermore, TRPM7 coprecipitated and colocalized with F-actin and α-actinin-1 at the growth cone. We conclude that calcium influx through TRPM7 inhibits axonal outgrowth and maturation by regulating the F-actin and α-actinin-1 protein complex. Inhibition of TRPM7 channel promotes axonal outgrowth, suggesting its therapeutic potential in neurodegenerative disorders.
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Toronto, 1132 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.|Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Turlova
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Toronto, 1132 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.|Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
authors.forename: Christine Y J
authors.initials: CYJ
authors.lastname: Bae
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
authors.forename: Marielle
authors.initials: M
authors.lastname: Deurloo
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Toronto, 1132 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.|Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Barszczyk
authors.affiliation: College of Natural and Computational Sciences, Hawaii Pacific University, Kaneohe, HI, 96744, USA.
authors.forename: F David
authors.initials: FD
authors.lastname: Horgen
authors.affiliation: Center for Biomedical Research, The Queen's Medical Center, Honolulu, HI, 96720, USA.|University of Hawaii Cancer Center and John A. Burns School of Medicine, Honolulu, HI, 96720, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fleig
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. zp.feng@utoronto.ca.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Feng
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Toronto, 1132 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. hss.sun@utoronto.ca.|Department of Physiology, Faculty of Medicine, University of Toronto, 3306 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. hss.sun@utoronto.ca.|Department of Pharmacology & Toxicology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. hss.sun@utoronto.ca.|Institute of Medical Science, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. hss.sun@utoronto.ca.
authors.forename: Hong-Shuo
authors.initials: HS
authors.lastname: Sun
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000085:Acetates; D004224:Diterpenes; D050053:TRPM Cation Channels; C568854:waixenicin A; C421903:Trpm7 protein, mouse
keywords: Axonal development; Ion channel; Neurite outgrowth; Neuronal maturation; TRPM7