title: Developmental changes in the regulation of calcium-dependent neurite outgrowth.
abstract: Intracellular calcium ions (Ca(2+)) have an essential role in the regulation of neurite outgrowth, but how outgrowth is controlled remains largely unknown. In this study, we examined how the mechanisms of neurite outgrowth change during development in chick and mouse dorsal root ganglion neurons. 2APB, a potent inhibitor of inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)R), inhibited neurite outgrowth at early developmental stages, but not at later stages. In contrast, pharmacological inhibition with Ni(2+), Cd(2+), or dantrolene revealed that ryanodine receptor (RyR)-mediated Ca(2+)-induced Ca(2+) release (CICR) was involved in neurite outgrowth at later stage, but not at early stages. The distribution of IP(3)R and RyR in growth cones also changed during development. Furthermore, pharmacological inhibition of the Ca(2+)-calmodulin-dependent phosphatase calcineurin with FK506 reduced neurite outgrowth only at early stages. These data suggest that the calcium signaling that regulates neurite outgrowth may change during development from an IP(3)R-mediated pathway to a RyR-mediated pathway.
authors.affiliation: Departments of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Arie
authors.forename: Masumi
authors.initials: M
authors.lastname: Iketani
authors.forename: Ken
authors.initials: K
authors.lastname: Takamatsu
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Takei
mesh_terms: D000818:Animals; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D005727:Ganglia, Spinal / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D016501:Neurites / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D065095:Calcineurin Inhibitors; D002147:Calmodulin; D002118:Calcium; D016559:Tacrolimus