FUNCTIONAL DOMAINS OF LAG-2, A PUTATIVE SIGNALING LIGAND FOR LIN-12 AND GLP-1 RECEPTORS IN CAENORHABDITIS-ELEGANS

The LAG-2 membrane protein is a putative signaling ligand for the LIN- 12 and GLP-1 receptors of Caenorhabditis elegans. LAG-2, like its Dros ophila homologues Delta and Serrate, acts in a conserved signal transd uction pathway to regulate cell fates during development. In this arti cle, we investigate the functional domains of LAG-2. For the most part , mutants were constructed in vitro and assayed for activity in transg enic animals. We find a functional role for all major regions except o ne. Within the extracellular domain, the N-terminal region, which bear s no known motif, and the DSL domain are both required. By contrast, t he region bearing epidermal growth factor-like repeats can be deleted with no apparent reduction in rescuing activity. The intracellular reg ion is not required for activity but instead plays a role in down-regu lating LAG-2 function. Finally, membrane association is critical for m utant rescue.