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

Autor:	Bean BDM; Centre for Molecular Medicine and Therapeutics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, Canada., Dziurdzik SK; Centre for Molecular Medicine and Therapeutics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, Canada., Kolehmainen KL; Centre for Molecular Medicine and Therapeutics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada.; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada., Fowler CMS; Centre for Molecular Medicine and Therapeutics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada., Kwong WK; Centre for Molecular Medicine and Therapeutics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada., Grad LI; Centre for Molecular Medicine and Therapeutics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, Canada., Davey M; Centre for Molecular Medicine and Therapeutics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada., Schluter C; Centre for Molecular Medicine and Therapeutics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada., Conibear E; Centre for Molecular Medicine and Therapeutics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada conibear@cmmt.ubc.ca.; Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2018 Oct 01; Vol. 217 (10), pp. 3593-3607. Date of Electronic Publication: 2018 Jul 17.
DOI:	10.1083/jcb.201804111
Abstrakt:	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. (© 2018 Bean et al.)
Databáze:	MEDLINE
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