Rho-and Ca2+- dependent signaling mechanisms controlling neuronal actin cytoskeleton

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1) Elucidation of the role of a Rho-target mDia in the regulation of axon elongationWe sought for Rho target molecules potentially involved in formation of polarity and bipolar axons out of the newly differentiated yet round cerebellar granule neurons in culture. Lipofection of various mutants revealed that 1) inhibition of ROCK activity promoted axon initiation and growth cone dynamics, and that 2) the adaptor mDia downstream of Rho rather promoted axon formation and elongation. Such experiments clearly demonstrated the necessity to orchestrate and coordinate the activity of several Rho effectors in order to achieve proper neurites. These findings are in press in J. Cell Biol.2) Molecular cloning and characterization of CLICK-III, a novel CaMK-Like CREB kinase candidate gene product.Activation of the transcription factor CREB is thought to play an important role in mediating long-term changes in neuronal properties by virtue of controlling activity-induced gene expression. We attempted to identify possible CaMKIV-related kinase with CREB phoshporylating activity. An isolated novel gene, CLICK-III, was activated in vitro by Ca2+/CaM, and was able to phosphorylate Ser-133 of CREB. CLICK-III expression was enriched in the limbic system and the midbrain, as revealed by in situ hybridization analyzes. This stands out from all published distribution of. Various other CaMK family members, and indicate the possibility that this kinase activity may possibly be involved in the activity of these nuclei. These findings are now in press in the J. Biol. Chem.