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Here we show that direct elevation of cytoplasmic Ca<jats:sup>2+<\/jats:sup>by extracellular application of a low concentration of ryanodine, which activated Ca<jats:sup>2+<\/jats:sup>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<jats:italic>Xenopus<\/jats:italic>spinal cord neurons. Furthermore, Ca<jats:sup>2+<\/jats:sup>-induced GTPase activity correlated with activation of protein kinase C and required a basal activity of Ca<jats:sup>2+<\/jats:sup>\/calmodulin-dependent protein kinase II. Thus, Rho GTPases may mediate axon guidance by linking upstream Ca<jats:sup>2+<\/jats:sup>signals triggered by guidance factors to downstream cytoskeletal rearrangements.<\/jats:p>","DOI":"10.1523\/jneurosci.4889-04.2005","type":"journal-article","created":{"date-parts":[[2005,3,2]],"date-time":"2005-03-02T22:13:18Z","timestamp":1109801598000},"page":"2338-2347","source":"Crossref","is-referenced-by-count":117,"title":["Ca<sup>2+<\/sup>-Dependent Regulation of Rho GTPases Triggers Turning of Nerve Growth 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