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

Competitive organelle-specific adaptors recruit Vps13 to membrane contact sites.

Author information

1
Centre for Molecular Medicine and Therapeutics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada.
2
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
3
Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada.
4
Centre for Molecular Medicine and Therapeutics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada conibear@cmmt.ubc.ca.

Abstract

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.

PMID:
30018089
PMCID:
PMC6168272
[Available on 2019-04-01]
DOI:
10.1083/jcb.201804111

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