Ca ++ /calmodulin-dependent protein kinase II (CAMKII) is thought to participate in mammalian learning based on transgenic and knockout mouse studies 1 however, the mechanism of CAMKII function in this process has not been elucidated. The phosphorylation of many gene products has been attributed to CaMKII based on in vitro assays, but in vivo evidence for these interactions is minimal. UNC-43, the C. elegans homolog of CAMKII, is 83% identical in the kinase domain to the mammalian CAMKII, suggesting that the targets of this kinase will also be conserved. We are using a genetic approach to identify in vivo targets of
unc-43. A kinase-activated allele of
unc-43,
n498, causes defects in egglaying, locomotion, and defecation. We reasoned that loss-of-function mutations in targets of
unc-43 would suppress one or more of the
unc-43(
n498) phenotypes. From a screen of 28,000 EMS-mutagenized haploid genomes, 19 recessive extragenic suppressors were isolated and placed into four complementation groups. The mutations in these four groups affect
goa-1 (4 alleles), the alpha subunit of an heterotrimeric Go protein 2 ,
dgk-1 /
sag-1( 4 alleles), a diacylglycerol kinase 3 ,
eat-16 /
sag-2 (4 alleles), an RGS protein 4 , and
eat-11 (7 alleles) 5 . As single mutants, these genes cause hyperactive locomotion and early egglaying. Mutations in each of these genes suppress the
unc-43(
n498) locomotion and egg-laying defects partially, consistent with
unc-43 acting directly on two or more of the genes, or with
unc-43 acting in parallel to these genes in the control of egglaying and locomotion. We are currently attempting to distinguish between these two models for
unc-43 function. 1 Silva, A. et al 1992 Science. Mayford, M. et al 1995 Cell. 2 Lochrie, M.A. et al 1991 Cell Regulation. Mendel, J.E. et al 1995 Science. Segalat, L. et al 1995 Science. 3 Nurrish, S. et al 1997 International Worm Meeting Abstracts. Chen, W. et al 1997 International Worm Meeting Abstracts. 4 Avery, L. 1993 Genetics. Chen, W. et al 1998 West Coast Worm Meeting Abstracts and Personal Communication. 5 Avery, L. 1993 Genetics.