ADAMs are integral membrane proteins which contain a d isintegrin a nd m etalloprotease domain, and have the potential to participate in proteolysis, adhesion, fusion and signaling events. So far thirty ADAM genes have been described from across the animal kingdom, but their precise functions and mechanisms remain largely unknown. A small number of mammalian ADAMs however, have been shown to be important in development, signal transduction, sperm and egg binding and muscle cell fusion. In addition, some C. elegans ADAMs have been investigated recently and these are thought to be involved in sperm and epithelial cell fusion events (
adm-1 ), in early embryonic development (
adm-2 ), and in vulval development (
sup-17 ). C. elegans also possesses homologues of ADAM-like genes known as ADAM-TS. Proteins encoded by this gene family are not membrane bound and have an additional thrombospondin-like motif, for example GON-1 and MIG-17. These proteins play essential roles in the morphogenesis of the C. elegans gonad. We are studying three other ADAMs genes in C. elegans :
adm-4 (a tumour necrosis factor alpha converting enzyme or TACE homologue); and two soluble ADAM-TSs, ( C02B4.1 and T19D2.1 ). GFP reporter data indicates that
adm-4 is highly expressed in most tissues in all post-embryonic stages. The expression pattern for C02B4.1 :: GFP however is more confined and is observed in body wall and pharyngeal muscle. We aim to complement the reporter data with RNAi/knockout mutagenesis work, but our main goal is to biochemically analyse the recombinant proteins in a mammalian expression system. Using this approach we hope to identify which proteins are cleaved by these ADAMs proteins, as well as providing information about their targeting and processing. Ultimately we hope to elucidate their physiological function and relate this information to mammalian ADAM proteins.