Ca2+/calmodulin-dependent protein kinases II and IV both promote survival but differ in their effects on axon growth in spiral ganglion neurons.

Spiral ganglion neuron (SGN) survival in vitro can be maintained by neurotrophins, permeant cAMP analogs, and depolarization in an additive manner, with depolarization being the most efficacious. Therefore, we used cultured SGNs to determine the mechanism by which depolarization promotes neuronal survival. Our data implicate Ca(2+)/calmodulin-dependent protein kinase (CaMK) activity by showing that it is induced by depolarization, that CaMK activity is necessary for at least part of the survival-promoting effect of depolarization, and that CaMKII or CamKIV activity suffices to support neuronal survival in the absence of other trophic stimuli. First, that depolarization of SGNs activates CaMKs is evidenced by observation of increased CaMKII phosphorylation and of CaMK-dependent CREB phosphorylation. Second, the requirement for CaMKs is shown by a reduction of SGN survival under depolarizing conditions in the presence of CaMK inhibitors. Third, transfection of COOH-terminal-truncated (lacking regulatory domain), constitutively active CaMKII or CaMKIV, but not of normal, full-length CAMKs, promotes SGN survival in the absence of other trophic stimuli, indicating that CaMK activity is sufficient to promote survival. The survival-promoting effect of truncated CaMKs is additive with that of depolarization, neurotrophins, or cyclic AMP. Although both CaMKII and CaMKIV activities converge in promoting survival, their actions on axon growth are markedly different: Transfection of truncated CaMKII, but not of truncated CaMKIV, into SGNs prevents axon outgrowth. Copyright 2003 Wiley-Liss, Inc.

Citation

Marlan R Hansen, Jinwoong Bok, Anand K Devaiah, Xiang-Ming Zha, Steven H Green. Ca2+/calmodulin-dependent protein kinases II and IV both promote survival but differ in their effects on axon growth in spiral ganglion neurons. Journal of neuroscience research. 2003 Apr 15;72(2):169-84

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PMID: 12671991

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