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

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 processes. Activation of the multisubunit kinase by calcium is effectively cooperative and can persist long after transient calcium rises. Despite extensive biochemical characterization of CaMKII and identification of numerous in vitro kinase targets, 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.

A Genetic Survey of Fluoxetine Action on Synaptic Transmission in Caenorhabditis elegans

“…It has been reported that unc-43 loss-and gain-of-function mutations cause, respectively, hypo-and hypercontraction of the bodywall muscles (Reiner et al 1995(Reiner et al , 1999. Indeed, the unc-43(n498)g f mutant displayed densely packed MYO-3T GFP muscle fibers (Figure 2c).…”

Cell Excitability Necessary for Male Mating Behavior inCaenorhabditis elegansIs Coordinated by Interactions Between Big Current and Ether-A-Go-Go Family K+ Channels

“…CaM-KII is a calcium-activated protein and is known to influence gene expression (Kapiloff et al 1991;Ramirez et al 1997;Hughes et al 2001;Zhang et al 2004;Ronkainen et al 2011). In C. elegans, loss-of-function mutations in CaMKII/ unc-43 have profound deleterious effects on virtually every behavior of the worm (Reiner et al 1999). The unc-43 (sy574) allele we previously isolated causes males to display the Prc phenotype, but does not have any gross effect on other behaviors in males or hermaphrodites (LeBoeuf et al 2007(LeBoeuf et al , 2011.…”

“…unc-43 encodes CaMKII in C. elegans and regulates movement, defecation, and egg laying in addition to its role in male mating (Reiner et al 1999). We previously reported that loss-of-function mutations in CaM-KII cause C. elegans males to display the Prc phenotype.…”

“…To test this hypothesis, we measured the transcript levels of genes involved in regulating the excitability of cells used in male mating behavior and also of genes involved in more general cell processes. We analyzed acr-18 [nicotinic acetylcholine receptor (nAChR) a-subunit], gar-3 (ACh receptor coupled to ga q ), unc-29 (nAChR non-a-subunit), unc-43 (CaMKII), and cat-2 (tyrosine hydroxylase) as candidate genes that are enriched in excitable cells (Sulston et al 1975;Fleming et al 1997;Hwang et al 1999;Lints and Emmons 1999;Reiner et al 1999;Sze et al 2000;Garcia et al 2001;Mongan et al 2002;LeBoeuf et al 2007;Liu et al 2007bLiu et al , 2011. Neither acr-18 nor cat-2 transcript levels were increased in males as compared to hermaphrodites (Figure 3, C and D), although both were reduced in slo-1(rg432) males.…”

Caenorhabditis elegans OSR-1 Regulates Behavioral and Physiological Responses to Hyperosmotic Environments

“…Interestingly, we find that osr-1(rm1), pmk-1(RNAi) (N ϭ gate the potential relationship between OSR-1 and the most upstream component of the Nsy pathway, UNC-175); nsy-1(ky379), osr-1(RNAi) (N ϭ 1259); and sek-1 (km4), osr-1(RNAi) (N ϭ 376) animals remained resis-43. As shown in Figure 5A, UNC-43, the only identified CaMKII in C. elegans (Reiner et al 1999), was also retant to the acute effects of osmotic stress by maintaining normal swimming behavior (100% motile animals after quired for viability under chronic osmotic stress.…”