Competitive organelle-specific adaptors recruit Vps13 to membrane contact sites

J Cell Biol. 2018 Oct 1;217(10):3593-3607. doi: 10.1083/jcb.201804111. Epub 2018 Jul 17.


The regulated expansion of membrane contact sites, which mediate the nonvesicular exchange of lipids between organelles, requires the recruitment of additional contact site proteins. Yeast Vps13 dynamically localizes to membrane contacts that connect the ER, mitochondria, endosomes, and vacuoles and is recruited to the prospore membrane in meiosis, but its targeting mechanism is unclear. In this study, we identify the sorting nexin Ypt35 as a novel adaptor that recruits Vps13 to endosomal and vacuolar membranes. We characterize an interaction motif in the Ypt35 N terminus and identify related motifs in the prospore membrane adaptor Spo71 and the mitochondrial membrane protein Mcp1. We find that Mcp1 is a mitochondrial adaptor for Vps13, and the Vps13-Mcp1 interaction, but not Ypt35, is required when ER-mitochondria contacts are lost. All three adaptors compete for binding to a conserved six-repeat region of Vps13 implicated in human disease. Our results support a competition-based model for regulating Vps13 localization at cellular membranes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism*
  • Humans
  • Mitochondrial Membranes / metabolism*
  • Models, Biological*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*


  • Carrier Proteins
  • SPO71 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • VPS13 protein, S cerevisiae