biostudies-literatureUnknown110(10)Balderhaar HJMembrane fusion along the endocytic pathway occurs in a sequence of tethering, docking, and fusion. At endosomes and vacuoles, the CORVET (class C core vacuole/endosome tethering) and HOPS (homotypic fusion and vacuole protein sorting) tethering complexes require their organelle-specific Rabs for localization and function. Until now, despite the absence of experimental evidence, it has been assumed that CORVET is a membrane-tethering factor. To test this theory and understand the mechanistic analogies with the HOPS complex, we set up an in vitro system, and establish CORVET as a bona-fide tether for Vps21-positive endosome/vacuole membranes. Purified CORVET binds to SNAREs and Rab5/Vps21-GTP. We then demonstrate that purified CORVET can specifically tether Vps21-positive membranes. TetheriProceedings of the National Academy of Sciences of the United States of America3823-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC3593874biostudies-literatureThe CORVET complex promotes tethering and fusion of Rab5/Vps21-positive membranes.PMC3593874Balderhaar HJYavavli EBrocker CLurick ALachmann JUngermann CfalseThe CORVET complex promotes tethering and fusion of Rab5/Vps21-positive membranes.Membrane fusion along the endocytic pathway occurs in a sequence of tethering, docking, and fusion. At endosomes and vacuoles, the CORVET (class C core vacuole/endosome tethering) and HOPS (homotypic fusion and vacuole protein sorting) tethering complexes require their organelle-specific Rabs for localization and function. Until now, despite the absence of experimental evidence, it has been assumed that CORVET is a membrane-tethering factor. To test this theory and understand the mechanistic analogies with the HOPS complex, we set up an in vitro system, and establish CORVET as a bona-fide tether for Vps21-positive endosome/vacuole membranes. Purified CORVET binds to SNAREs and Rab5/Vps21-GTP. We then demonstrate that purified CORVET can specifically tether Vps21-positive membranes. Tetheri2013-01-01T00:00:00Z2013 Mar2025-04-19T09:06:05.192Z2019-03-27T01:05:53ZS-EPMC35938742341730710.1073/pnas.1221785110