p24 proteins and quality control of LIN-12 and GLP-1 trafficking in Caenorhabditis elegans

Mutations in the Caenorhabditis elegans sel-9 gene elevate the activity of lin-12 and glp-1, which encode members of the LIN-12/NOTCH family of recept ors, Sequence analyis indicates SEL-9 is one of several C. elegans p24 prot eins. Allele-specific genetic interactions suggest that reducing sel-9 acti vity increases the activity of mutations altering the extracellular domains of LIN-12 or GLP-1, Reducing sel-9 activity restores the trafficking to th e plasma membrane of a mutant GLP-1 protein that would otherwise accumulate within the cell. Our results suggest a role for SEL-9 and other p24 protei ns in the negative regulation of transport of LIN-12 and GLP-1 to the cell surface, and favor a role for p24 proteins in a quality control mechanism f or endoplasmic reticulum-Golgi transport.