Membrane protein retention in the yeast Golgi apparatus: dipeptidyl aminopeptidase A is retained by a cytoplasmic signal containing aromatic residues

Of the yeast Golgi membrane proteins examined thus far, all are retained via their cytoplasmic domains. Our laboratory has focused on the mechanism of targeting and retention of dipeptidyl aminopeptidase (DPAP) I A, a type II yeast Golgi membrane protein (i.e., NH2-terminal cytoplasmic domain, single membrane anchor, and a large lumenal domain). DPAP A is one of three resident Golgi proteases (along with Kexlp and Kex2p) that process the secreted mating pheromone u-factor (Fuller et al., 1988) in a late Golgi compartment (Julius et al., 1984; Graham and Emr, 1991; Roberts et al., 1992) . Previous work has shown that the ll8-amino acid cytoplasmic domain of DPAP A is necessary and sufficient for its retention in the Golgi apparatus (Roberts et al., 1992) . Mutations in the cytoplasmic domain of DPAP A, as well as overproduction of the protein, resulted in its mislocalization to the vacuole, not the plasma membrane. These observations, along with the fact that no single domain of the vacuolar membrane protein, DPAP B, was required for vacuolar targeting, led us to propose the vacuolar default model for membrane protein sorting in the yeast secretory pathway (Roberts et al., 1990 (Roberts et al., , 1992 . This model states that no sorting information is required for transport of membrane proteins to the vacuole, and positive sorting information is required for nonvacuolar membrane proteins to stay out of the vacuole. Consistent with this model are the observations that the cytoplasmic domains of Kexlp (Cooper and Bussey, 1992) and Kex2p (Fuller et al., 1989; Wilcox et al., 1992) are necessary for Golgi retention and that nonretained Kexlp and Kex2p are mislocalized to the vacuolar membrane. It is important to note that the vacuolar default model does not apply to soluble proteins of the yeast secretory pathway, which are known to be secreted by default (Burgess and Kelly, 1987; Pelham, 1989) .