Mutations in a C. elegans Gqα Gene Disrupt Movement, Egg Laying, and Viability

tively, are 82% and 66% identical to their mouse and rat counterparts. are worm specific G␣'s that do not correspond to any particular mammalian ␣ subunit (Lochrie et al., 1991). In addition, one G␤ subunit has been identified in C. ele-gans (van der Voorn et al., 1990). Dallas, Texas 75235 We have examined the function of Gq␣ in C. elegans. The mammalian Gq␣ family is comprised of four members , Gq␣, G11␣, G14␣, and G15␣, which together account Summary for the major component of G protein–mediated signal-ing through phosphoinositides (Lee et al., 1992). In mam-We find that C. elegans egl-30 encodes a heterotri-mals, G q ␣ and G 11 ␣ are expressed in almost all tissues meric G protein ␣ subunit more than 80% identical to (Strathmann and Simon, 1990; Wilkie et al., 1991), con-mammalian G q␣ family proteins, and which can func-sistent with the diverse processes in which they have tion as a G q␣ subunit in COS-7 cells. We have identified been implicated, including synaptic transmission, con-new egl-30 alleles in a selection for genes involved traction of smooth muscle, recruitment of immune cells, in the C. elegans acetylcholine response. Two egl-30 growth control, and cell migration during development alleles specify premature termination of G q ␣ and are essentially lethal in homozygotes. Animals homozy-G14␣ and G15␣ show much more restricted expression. gous for six other egl-30 alleles are viable and fertile, At least 30 different receptors can activate Gq and G11 but exhibit delayed egg laying and leave flattened including receptors for the neurotransmitters acetylcho-tracks. Overexpression of the wild-type egl-30 gene line, serotonin and glutamate (Watson and Arkinstall, produces the opposite behavior. Analysis of these mu-1994), all of which are present in C. elegans. Mutations tants suggest that their phenotypes reflect defects in in several Gq/11 specific receptors have been identified the muscle or neuromuscular junction. in human disease (Baldwin, 1994); however, genomic mutations that produce visible effects have not been Introduction identified in the G q ␣ family itself. Thus, the full spectrum of G q function, especially in development, has not been Heterotrimeric G proteins receive signals from a diverse directly explored. set of extracellular receptors and convert them into a In this study, we have identified the gene encoding a limited set of intracellular responses. G proteins are C. elegans homolog of the G q ␣ family and determined composed of three subunits: the ␣ …