CIS-ACTING AND TRANS-ACTING FUNCTIONS REQUIRED FOR ENDOCYTOSIS OF THEYEAST PHEROMONE RECEPTORS

The Saccharomyces cerevisiae a-factor receptor (STE3) is subject to tw o modes of endocytosis: a constitutive process that occurs in the abse nce of ligand and a regulated process that is triggered by binding of ligand. Both processes result in delivery of the receptor to the vacuo le for degradation. Receptor mutants deleted for part of the COOH-term inal cytoplasmic domain are disabled for constitutive, but not ligand- dependent internalization. Trans-acting mutants that impair constituti ve endocytosis have been isolated. One of these, ren1-1, is blocked at a late step in the endocytic pathway, as receptor accumulates in a pr evacuolar endosome-like compartment. REN1 is identical to VPS2, a gene required for delivery of newly synthesized vacuolar enzymes to the va cuole. Based on this identity, we suggest a model in which the transpo rt pathways to the vacuole-the endocytic pathway and the vacuolar biog enesis pathway-merge at an intermediate endocytic compartment. As rece ptor also accumulates at the surface of ren1 cells, receptor may recyc le from the putative endosome to the surface, or REN1 may also be requ ired to carry out an early step in endocytosis.