VPS13Regulates Membrane Morphogenesis During Sporulation inSaccharomyces cerevisiae

Abstract

The hereditary disorders chorea acanthocytosis and Cohen syndrome are caused by mutations in different members of a family of genes that are orthologs of yeast VPS13. In vegetatively growing yeast, VPS13 is involved in the delivery of proteins to the vacuole. During sporulation, VPS13 is important for formation of the prospore membrane that encapsulates the daughter nuclei to give rise to spores. We report that VPS13 is required for multiple aspects of prospore membrane morphogenesis. 1) VPS13 promotes expansion of the prospore membrane via regulation of phosphatidylinositol-phosphates, that in turn activate the phospholipase D, Spo14; 2) VPS13 is required for a late step in cytokinesis at the cell division that gives rise to spores; and 3) VPS13 regulates a membrane bending activity that generates intralumenal vesicles. These results demonstrate that Vps13 plays a broader role in membrane biology than previously known, which may have important implications for the functions of VPS13 orthologs in humans.