STRUCTURE, FUNCTION, AND EXPRESSION OF SEL-1, A NEGATIVE REGULATOR OFLIN-12 AND GLP-1 IN C-ELEGANS

Previous work indicated that sel-1 functions as a negative regulator o f lin-12 activity, and predicted that SEL-1 is a secreted or membrane associated protein. In this study, we describe cell ablation experimen ts that suggest sel-1 mutations elevate lin-12 activity cell autonomou sly. We also use transgenic approaches to demonstrate that the predict ed signal sequence of SEL-1 can direct secretion and is important for function, while a C-terminal hydrophobic region is not required for SE L-1 function. In addition, by analyzing SEL-1 localization using speci fic antisera we find that SEL-1 is localized intracellularly, with a p unctate staining pattern suggestive of membrane bound vesicles. We inc orporate these observations, and new information about a related yeast gene, into a proposal for a possible mechanism for SEL-1 function in LIN-12 turnover.