PT  - JOURNAL ARTICLE
AU  - Ming Jin
AU  - Chen-bing Guan
AU  - Yun-ai Jiang
AU  - Gang Chen
AU  - Chun-tao Zhao
AU  - Kai Cui
AU  - Yuan-quan Song
AU  - Chien-ping Wu
AU  - Mu-ming Poo
AU  - Xiao-bing Yuan
TI  - Ca<sup>2+</sup>-Dependent Regulation of Rho GTPases Triggers Turning of Nerve Growth Cones
AID  - 10.1523/JNEUROSCI.4889-04.2005
DP  - 2005 Mar 02
TA  - The Journal of Neuroscience
PG  - 2338--2347
VI  - 25
IP  - 9
4099  - http://www.jneurosci.org/content/25/9/2338.short
4100  - http://www.jneurosci.org/content/25/9/2338.full
SO  - J. Neurosci.2005 Mar 02; 25
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.