RT Journal Article SR Electronic T1 Ca2+-Dependent Regulation of Rho GTPases Triggers Turning of Nerve Growth Cones JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 2338 OP 2347 DO 10.1523/JNEUROSCI.4889-04.2005 VO 25 IS 9 A1 Jin, Ming A1 Guan, Chen-bing A1 Jiang, Yun-ai A1 Chen, Gang A1 Zhao, Chun-tao A1 Cui, Kai A1 Song, Yuan-quan A1 Wu, Chien-ping A1 Poo, Mu-ming A1 Yuan, Xiao-bing YR 2005 UL http://www.jneurosci.org/content/25/9/2338.abstract AB 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.