CONTROL OF CELL FATE IN C-ELEGANS BY A GLP-1 PEPTIDE CONSISTING PRIMARILY OF ANKYRIN REPEATS

THE homologous proteins GLP-1 and LIN-12 are required for cell interac tions during nematode development1-5. glp-1 and lin-12 are members of a gene family that includes Drosophila Notch and several vertebrate ho mologues6. The members of this family have a single transmembrane doma in and a similar arrangement of repeated amino-acid motifs (see Fig. 1 ). The mechanism by which proteins in this family function is not unde rstood. One hypothesis is that these proteins are receptors, each with an extracellular domain that binds a ligand and an intracellular doma in that influences the activity of downstream cell fate regulators. He re we report that a region of the GLP-1 intracellular domain, consisti ng primarily of six ankyrin repeats, is sufficient to direct cell fate . The cell fate transformations seen are similar to transformations ca used by gain-of-function mutations in either glp-1 or lin-12 and do no t rely on endogenous lin-12 or glp-1 activity. We propose that the ank yrin repeat region of GLP-1 is responsible for controlling downstream regulators of cell fate.