Studies on Rho-and Ca^<2+>-dependent signaling mechanisms regulating neuronal actin cytoskeleton

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1.We examined the signaling pathway downstream of Rho that may be involved in regulating axonogenesis in cerebellar granule neurons in primary culture. These were chosen because these neurons have the interesting property of generating two bipolar axons immediately after plating, prior to further development of neurites, thereby greatly facilitating signaling analyses. We elucidated the essential positive role of the SDF-1α/Rho/mDial pathway in controlling the rate of axon elongation. As we previously discovered a negative regulatory role for the Rho/ROCK cascade, our data suggest that appropriate rate of axonogenesis might be tightly controlled by an antagonism between two distinct Rho effectors, ROCK and mDia1.2.We previously described how synaptic activity-induced calcium mobilization in hippocampal pyramidal neurons triggered actin recruitment to the spines. However, the critical molecules linking calcium with local actin reorganization remained unclear. We here examine whether a novel CaMK we identified as CLICK-III/CaMKIγ was potentially able to fill this role. When overexpressed in vitro, CLICK-III/CaMKIγ was found to be sufficient in promoting and facilitating depolarization-induced neuritogenesis in PC-12 cells.