Vulval precursor cells (VPCs) of C. elegans have the potential,through reciprocal LIN-12/Notch and LET-23/EGFR signalling, to give rise to either vulval or nonvulval fates. In VPCs in which LET-23 is activated maximally, LIN-12 is endocytosed and degraded. Now on , Iva Greenwald and co-workers report the isolation of SEL-2, a C. elegans homologue of mammalian neurobeachin (which is required for neurotransmission at neuromuscular junctions) and LRBA (which positively regulates EGFR in cell culture). SEL-2, they show, is required for efficient endocytosis in epithelial cells and for maintaining LIN-12 in a steady state. LIN-12 is mislocalised basolaterally in sel-2 mutants and cannot be degraded in response to Ras activation. Moreover, endocytosis is compromised in the intestinal epithelium of these mutants, as revealed by the basolateral accumulation of a dye that marks endocytic vesicles. In VPCs, LIN-12 trafficking and stability, rather than its transcription, is modulated, and SEL-2's role may contribute to the mechanisms required for these processes and for cell fate specification.
