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 interactions during nematode development. glp-1 and lin-12 are members of a gene family that includes Drosophila Notch and several vertebrate homologues. The members of this family have a single transmembrane domain and a similar arrangement of repeated amino-acid motifs (see Fig. 1). The mechanism by which proteins in this family function is not understood. One hypothesis is that these proteins are receptors, each with an extracellular domain that binds a ligand and an intracellular domain that influences the activity of downstream cell fate regulators. Here we report that a region of the GLP-1 intracellular domain, consisting primarily of six ankyrin repeats, is sufficient to direct cell fate. The cell fate transformations seen are similar to transformations caused by gain-of-function mutations in either glp-1 or lin-12 and do not rely on endogenous lin-12 or glp-1 activity. We propose that the ankyrin repeat region of GLP-1 is responsible for controlling downstream regulators of cell fate.