Abstract
Calcium/calmodulin-dependent serine/threonine kinase type II (CaMKII) is one of the most abundant proteins in the mammalian brain, where it is thought to regulate synaptic plasticity and other processes1,2,3. Activation of the multisubunit kinase4 by calcium is effectively cooperative and can persist long after transient calcium rises1,5,6. Despite extensive biochemical characterization of CaMKII and identification of numerous in vitro kinase targets1, little is known about its function in vivo. Here we report that unc-43 encodes the only Caenorhabditis elegans CaMKII. A gain-of-function unc-43 mutation reduces locomotory activity, alters excitation of three muscle types and lengthens the period of the motor output of a behavioural clock. Null unc-43 mutations cause phenotypes generally opposite to those of the gain-of-function mutation. Mutations in the unc-103 potassium channel gene suppress a gain-of-function phenotype of unc-43 in one tissue without affecting other tissues; thus, UNC-103 may be a tissue-specific target of CaMKII in vivo.
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Acknowledgements
We thank I. Mori for strains and discussion of tax-4; T. Inoue for daf-14 cloning; J. Knapp for isolating sa402; K. Iwasaki, D. Johnstone, D. Liu, E. Malone, D. Weinshenker and the rest of our lab for discussions; G. Garriga and D. Johnstone for reading the manuscript; L. Griffith for 4A11 antibody; Y. Kohara for cDNA clones; A. Coulson for cosmid clones; H. R. Horvitz for unc-43 mutants; and B. Meyer for hospitality during the writing of this manuscript. Some strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH Center for Research Resources (NCRR). The work was funded by an NIH grant to J.H.T., and E.M.N. was supported by the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation.
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Reiner, D., Newton, E., Tian, H. et al. Diverse behavioural defects caused by mutations in Caenorhabditis elegans unc-43 CaM Kinase II. Nature 402, 199–203 (1999). https://doi.org/10.1038/46072
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DOI: https://doi.org/10.1038/46072
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