Diverse behavioural defects caused by mutations in Caenorhabditis elegans unc-43 CaM kinase II

Calcium/calmodulin-dependent serine/threonine kinase type II (CaMKII) is on e of the most abundant proteins in the mammalian brain, where it is thought to regulate synaptic plasticity and other processes(1-3). Activation of th e multisubunit kinase(4) by calcium is effectively cooperative and can pers ist long after transient calcium rises(1,5,6). Despite extensive biochemica l characterization of CaMKII and identification of numerous in vitro kinase targets(1), little is known about its function in vivo. Here we report tha t unc-43 encodes the only Caenorhabditis elegans CaMKII. A gain-of-function unc-43 mutation reduces locomotory activity, alters excitation of three mu scle types and lengthens the period of the motor output of a behavioural cl ock. Null unc-43 mutations cause phenotypes generally opposite to those of the gain-of-function mutation. Mutations in the unc-103 potassium channel g ene suppress a gain-of-function phenotype of unc-43 in one tissue without a ffecting other tissues; thus, UNC-103 may be a tissue-specific target of Ca MKII in vivo.