In mammals, heterotrimeric G proteins are classified into four families, Gi/Go, Gq, Gs and G12, based on similarity of their sequence and function. C. elegans
egl-30 encodes a G protein alpha subunit which is more than 80% identical to two members of the mammalian Gq alpha family(1). We are interested in genes which act in the
egl-30 pathway, as they may encode new regulators of G protein signaling.
eat-11 is one such gene.
eat-11 animals arrest at hatching in the presence of low levels of the cholinergic agonist arecoline(2) and mutations in
egl-30 strongly suppress this arecoline effect(1). We have found that
eat-11 animals exhibit behaviors which are opposite to
egl-30(r.f) animals in several respects.
egl-30(r.f.) animals move slowly and with reduced flexations, and lay few eggs in the presence of serotonin. By contrast,
eat-11 animals move more quickly than wild type animals and with exaggerated flexations. In addition,
eat-11 animals respond dramatically more strongly than N2 to serotonin in an egg laying assay. We hope to clarify the relationship between
egl-30 and
eat-11 by determining the molecular identity of the EAT-11 protein. To elucidate the G12 pathway in C. elegans, we are studying the gene
gpa-12, encoding a G12 alpha subunit on cosmid F18G5. In contrast to the other G protein families, the receptors and the second messengers involved in transduction of signals via the G12 family are largely unknown. Reexamination of expression patterns has shown that
gpa-12::gfp is expressed most strongly in the pharyngeal muscle and hypodermus. We have engineered a constitutively active allele of
gpa-12 under
hsp-16 control. When this allele is induced by heat shock during embryogenesis, animals hatch into uncoordinated, developmentally arrested larvae which eventually recover. We plan on exploiting this phenotype to identify
gpa-12 effectors in a genetic screen. (1) Brundage, L., Avery, L., Katz, A., Kim, U-J., Mendel, J.E., Sternberg, P. W., and Simon, M.I. (1996). Mutations in a C. elegans Gq a gene disrupt movement, egg laying, and viability. Neuron 16 : 999-1009. (2) Avery, L. (1993) The genetics of feeding in Caenorhabditis elegans. Genetics 133 : 897-917.