{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:36:45Z","timestamp":1777451805438,"version":"3.51.4"},"reference-count":57,"publisher":"American Society for Cell Biology (ASCB)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:p>Organization of lipids into membrane microdomains is a vital mechanism of protein processing. Here we show that overexpression of ERG6, a gene involved in ergosterol synthesis, elevates sterol levels 1.5-fold on the vacuole membrane and enhances their homotypic fusion. The mechanism of sterol-enhanced fusion is not via more efficient sorting, but instead promotes increased kinetics of fusion subreactions. We initially isolated ERG6 as a suppressor of a vrp1\u0394 growth defect selective for vacuole function. VRP1 encodes verprolin, an actin-binding protein that colocalizes to vacuoles. The vrp1\u0394 mutant has fragmented vacuoles in vivo and isolated vacuoles do not fuse in vitro, indicative of a Vrp1p requirement for membrane fusion. ERG6 overexpression rescues vrp1\u0394 vacuole fusion in a cytosol-dependent manner. Cytosol prepared from the vrp1\u0394 strain remains active; therefore, cytosol is not resupplying Vrp1p. Las17p (Vrp1p functional partner) antibodies, which inhibit wild-type vacuole fusion, do not inhibit the fusion of vacuoles from the vrp1\u0394-ERG6 overexpression strain. Vacuole-associated actin turnover is decreased in the vrp1\u0394 strain, but recovered by ERG6 overexpression linking sterol enrichment to actin remodeling. Therefore, the Vrp1p\/Las17p requirement for membrane fusion is bypassed by increased sterols, which promotes actin remodeling as part the membrane fusion mechanism.<\/jats:p>","DOI":"10.1091\/mbc.e04-03-0194","type":"journal-article","created":{"date-parts":[[2004,7,15]],"date-time":"2004-07-15T00:19:09Z","timestamp":1089850749000},"page":"4609-4621","source":"Crossref","is-referenced-by-count":21,"title":["Enhanced Membrane Fusion in Sterol-enriched Vacuoles Bypasses the Vrp1p Requirement"],"prefix":"10.1091","volume":"15","author":[{"given":"Kelly","family":"Tedrick","sequence":"first","affiliation":[{"name":"Department of Cell Biology, University of Alberta, Edmonton, Alberta, T6G 2H7 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Trischuk","sequence":"additional","affiliation":[{"name":"CIHR Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, T6G 2H7 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Lehner","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Alberta, Edmonton, Alberta, T6G 2H7 Canada"},{"name":"CIHR Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, T6G 2H7 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Eitzen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Alberta, Edmonton, Alberta, T6G 2H7 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1076","reference":[{"key":"REF1","doi-asserted-by":"crossref","unstructured":"Anderson, R.G., and Jacobson, K. 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Electrospray ionization tandem mass spectrometry (ESI-MS\/MS) analysis of the lipid molecular species composition of yeast subcellular membranes reveals acyl chain-based sorting\/remodeling of distinct molecular species en route to the plasma membrane.J. Cell Biol.146, 741-754.","DOI":"10.1083\/jcb.146.4.741"},{"key":"REF43","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.01-10-0512"},{"key":"REF44","unstructured":"Segev, N. (2001). Ypt\/rab GTPases: regulators of protein trafficking.Sci. STKE2001,RE11."},{"key":"REF45","doi-asserted-by":"crossref","unstructured":"Stamnes, M. (2002). Regulating the actin cytoskeleton during vesicular transport.Curr. Opin. Cell Biol.14, 428-433.","DOI":"10.1016\/S0955-0674(02)00349-6"},{"key":"REF46","doi-asserted-by":"crossref","unstructured":"Symons, M., and Rusk, N. (2003). Control of vesicular trafficking by Rho GTPases.Curr. 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