The VPS8 gene is required for localization and trafficking of the CPY sorting receptor in Saccharomyces cerevisiae

To better understand the process of protein sorting to the yeast vacuole, the VPS8 gene was identified and characterized. VPS8 encodes a membrane-associated hydrophilic protein of 135 kDa (Vps8p), which is required for the accurate sorting of the vacuolar hydrolase, carboxypeptidase Y (CPY). vps8 mutant cells missort and secrete CPY as well as a second soluble vacuolar hydrolase, proteinase A. In vps8 mutants, several late-Golgi membrane proteins fail to be retained in the Golgi apparatus. The Golgi-localized CPY sorting receptor, Vps10p, is mislocalized to and aberrantly proteolyzed in the vacuole. Based on our findings, we propose that Vps8p is part of a protein complex that associates with Golgi and post-Golgi membranes and functions in the retrieval of Golgi membrane proteins from the prevacuolar compartment.