VMA22P IS A NOVEL ENDOPLASMIC RETICULUM-ASSOCIATED PROTEIN REQUIRED FOR ASSEMBLY OF THE YEAST VACUOLAR H-ATPASE COMPLEX()

The Saccharomyces cerevisiae vacuolar H+-ATPase (V-ATPase) is a multi- subunit complex that can be structurally and functionally divided into peripheral (V-1) and integral membrane (V-0) sectors. The vma22-1 mut ation was isolated in a screen for mutants defective in V-ATPase funct ion. vma22 Delta cells contain no V-ATPase activity due to a failure t o assemble the enzyme complex; V-1 subunits accumulate in the cytosol, and the V-0 100-kDa subunit is rapidly degraded. Turnover of the 100- kDa integral membrane protein was found to occur in the endoplasmic re ticulum (ER) of vma22 Delta cells. The product of the VMA22 gene, Vma2 2p, is a 21-kDa hydrophilic protein that is not a subunit of the V-ATP ase but rather is associated with ER membranes. The association of Vma 22p with ER membranes was perturbed by mutations in VMA12, a gene that encodes an ER membrane protein (Vma12p) that is also required for V-A TPase assembly. These results indicate that Vma22p, along with Vma21p and Vma12p, form a set of ER proteins required for V-ATPase assembly.