Yeast Kex1p is a Golgi-associated membrane protein: deletions in a cytoplasmic targeting domain result in mislocalization to the vacuolar membrane

Kexlp is predicted to be a type I transmembrane protein with a large amino-terminal protease domain in the lumen of the secretory pathway, a single membrane-spanning domain, and a smaller carboxy-terminai domain positioned cytoplasmicaUy. The observation that KEX/cells intracellularly retain Kexlp activity prompted an analysis to determine in which secretory compartment Kexlp resided, and how it achieved such retention. Kexlp was found to be localized to the yeast Golgi apparatus, with retention mediated via the cytoplasmic domain of the protein. Removal of this domain or overproduction of wild-type Kexlp resulted in delivery of the protein to the vacuole rather than to the cell surface. This surprising result raises the possibility that the vacuole is the default destination for yeast Golgi membrane proteins.