title: Functional domains of LAG-2, a putative signaling ligand for LIN-12 and GLP-1 receptors in Caenorhabditis elegans.
abstract: 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 Drosophila homologues Delta and Serrate, acts in a conserved signal transduction pathway to regulate cell fates during development. In this article, we investigate the functional domains of LAG-2. For the most part, mutants were constructed in vitro and assayed for activity in transgenic animals. We find a functional role for all major regions except one. Within the extracellular domain, the N-terminal region, which bears no known motif, and the DSL domain are both required. By contrast, the region bearing epidermal growth factor-like repeats can be deleted with no apparent reduction in rescuing activity. The intracellular region is not required for activity but instead plays a role in down-regulating LAG-2 function. Finally, membrane association is critical for mutant rescue.
authors.affiliation: Howard Hughes Medical Institute, University of Wisconsin-Madison 53706, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Henderson
authors.forename: D
authors.initials: D
authors.lastname: Gao
authors.forename: S
authors.initials: S
authors.lastname: Christensen
authors.forename: J
authors.initials: J
authors.lastname: Kimble
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D002462:Cell Membrane / Q000235:genetics; D017353:Gene Deletion; D000067757:Glucagon-Like Peptide-1 Receptor; D015801:Helminth Proteins / Q000737:chemistry / Q000502:physiology*; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D018027:Receptors, Glucagon / Q000378:metabolism*; D051880:Receptors, Notch; D015398:Signal Transduction / Q000235:genetics; D013347:Subcellular Fractions / Q000378:metabolism; D019076:Transgenes
chemical_list: D029742:Caenorhabditis elegans Proteins; D000067757:Glucagon-Like Peptide-1 Receptor; D015801:Helminth Proteins; D008024:Ligands; C082460:Lin-12 protein, C elegans; D008565:Membrane Proteins; D018027:Receptors, Glucagon; D051880:Receptors, Notch; C086488:lag-2 protein, C elegans