James K. Phelan1, Kelvin Wong1, Sergio M. Pinto, Laurent Falquet3, Hans H. Jung4 and Michael O. Hengartner1. Mutations in
ced-8 were first identified in a screen for genes required for the timely engulfment of developmental cell corpses (Ellis, Jacobson, & Horvitz, 1991). Subsequent work clarified that the persistent corpses were the result of a delay in their generation, rather than a failure of engulfment (Stanfield & Horvitz, 2000). With ten predicted hydrophobic regions, CED-8 is anticipated to be a transmembrane protein and has been proposed to be a transporter. The function of
ced-8, however, remains undetermined. Our goals are to clarify the role of
ced-8 in cell corpse generation and clearance, and to utilize the mutation as a tool to identify additional genes with which
ced-8 interacts. We are in the process of mapping the spatiotemporal expression pattern of
ced-8 during the C. elegans lifecycle, and of experimentally determining the membrane topology of CED-8. Potential candidate interacting genes are being tested by double mutant and RNAi analysis. The resulting data will allow educated hypotheses to be formulated as to the function(s) of CED-8. In addition,
ced-8 is now known to be the sole C. elegans representative of a gene family with multiple members in mammals. The founding member of the gene family, XK, is mutated in McLeod syndrome, a neuroacanthocytosis disease in which a neuromuscular degeneration is found in association with altered red blood cell morphology. We are attempting to rescue the
ced-8 mutant phenotype by expression of representative mammalian cDNAs in order to ascertain which, if any, represent functional orthologs of CED-8.