INTRAGENIC DOMINANT SUPPRESSORS OF GLP-1, A GENE ESSENTIAL FOR CELL-SIGNALING IN CAENORHABDITIS-ELEGANS, SUPPORT A ROLE FOR CDC1O SWI6/ANKYRIN MOTIFS IN GLP-1 FUNCTION/

The glp-1 gene product mediates cell-cell interactions required for ce ll fate specification during development in Caenorhabditis elegans. To identify genes that interact with glp-1, we screened for dominant sup pressors of two temperature-sensitive glp-1 alleles and recovered 18 m utations that suppress both germline and embryonic glp-1 phenotypes. T hese dominant suppressors are tightly linked to glp-1 and do not bypas s the requirement for a distal tip cell, which is thought to be the so urce of a signal that is received and transduced by the GLP-1 protein. Using single-strand conformation polymorphism (SSCP) analysis and DNA sequencing, we found that at least 17 suppressors are second-site int ragenic revertants. The suppressors, like the original glp-1(ts) mutat ions, are all located in the cdc10/SWI6/ankyrin domain of GLP-1. cdc10 /SWI6/ankyrin motifs have been shown to mediate specific protein-prote in interactions in other polypeptides. We propose that the glp-1(ts) m utations disrupt contact between GLP-1 and an as yet unidentified targ et protein(s) and that the dominant suppressor mutations restore appro priate protein-protein interactions.