title: Ca2+-dependent regulation of rho GTPases triggers turning of nerve growth cones.
abstract: Cytoplasmic Ca2+ elevation and changes in Rho GTPase activity are both known to mediate axon guidance by extracellular factors, but the causal relationship between these two events has been unclear. Here we show that direct elevation of cytoplasmic Ca2+ by extracellular application of a low concentration of ryanodine, which activated Ca2+ release from intracellular stores, upregulated Cdc42/Rac, but downregulated RhoA, in cultured cerebellar granule cells and human embryonic kidney 293T cells. Chemoattractive turning of the growth cone triggered by a gradient of ryanodine was blocked by overexpression of mutant forms of Cdc42 but not of RhoA in Xenopus spinal cord neurons. Furthermore, Ca2+-induced GTPase activity correlated with activation of protein kinase C and required a basal activity of Ca2+/calmodulin-dependent protein kinase II. Thus, Rho GTPases may mediate axon guidance by linking upstream Ca2+ signals triggered by guidance factors to downstream cytoskeletal rearrangements.
authors.affiliation: Institute of Neuroscience, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, and Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Jin
authors.forename: Chen-bing
authors.initials: CB
authors.lastname: Guan
authors.forename: Yun-ai
authors.initials: YA
authors.lastname: Jiang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Chun-tao
authors.initials: CT
authors.lastname: Zhao
authors.forename: Kai
authors.initials: K
authors.lastname: Cui
authors.forename: Yuan-quan
authors.initials: YQ
authors.lastname: Song
authors.forename: Chien-ping
authors.initials: CP
authors.lastname: Wu
authors.forename: Mu-ming
authors.initials: MM
authors.lastname: Poo
authors.forename: Xiao-bing
authors.initials: XB
authors.lastname: Yuan
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D003952:Diagnostic Imaging / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004625:Embryo, Nonmammalian; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000494:pharmacology; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009414:Nerve Growth Factors / Q000494:pharmacology; D000075388:Netrin-1; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D012433:Ryanodine / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection / Q000379:methods; D025521:Tumor Suppressor Proteins / Q000494:pharmacology; D014981:Xenopus; D020764:cdc42 GTP-Binding Protein / Q000494:pharmacology; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D019208:Brain-Derived Neurotrophic Factor; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D009414:Nerve Growth Factors; D025521:Tumor Suppressor Proteins; C031815:toxB protein, Clostridium difficile; D049452:Green Fluorescent Proteins; D012433:Ryanodine; D000075388:Netrin-1; D004533:Egtazic Acid; D019284:Thapsigargin; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium
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