title: Class C ABC transporters andSaccharomyces cerevisiaevacuole fusion.
abstract: Membrane fusion is carried out by core machinery that is conserved throughout eukaryotes. This is comprised of Rab GTPases and their effectors, and SNARE proteins, which together are sufficient to drive the fusion of reconstituted proteoliposomes. However, an outer layer of factors that are specific to individual trafficking pathwaysin vivoregulates the spatial and temporal occurrence of fusion. The homotypic fusion ofSaccharomyces cerevisiaevacuolar lysosomes utilizes a growing set of factors to regulate the fusion machinery that include members of the ATP binding cassette (ABC) transporter family. Yeast vacuoles have five class C ABC transporters that are known to transport a variety of toxins into the vacuole lumen as part of detoxifying the cell. We have found that ABCC transporters can also regulate vacuole fusion through novel mechanisms. For instance Ybt1 serves as negative regulator of fusion through its effects on vacuolar Ca2+homeostasis. Additional studies showed that Ycf1 acts as a positive regulator by affecting the efficient recruitment of the SNARE Vam7. Finally, we discuss the potential interface between the translocation of lipids across the membrane bilayer, also known as lipid flipping, and the efficiency of fusion.
authors.affiliation: Department of Biochemistry; University of Illinois at Urbana-Champaign ; Urbana, IL USA.
authors.forename: Terry L
authors.initials: TL
authors.lastname: Sasser
authors.affiliation: Department of Biochemistry; University of Illinois at Urbana-Champaign ; Urbana, IL USA.
authors.forename: Rutilio A
authors.initials: RA
authors.lastname: Fratti
keywords: ABC, ATP binding cassette; Bpt1; Ca2+ homeostasis; DAG, diacylglycerol; HOPS, homotypic fusion and vacuole protein sorting complex; MDR, multidrug resistance; MSD, membrane spanning domain; NBD, nucleotide binding domain; Nft1; PA, phosphatidic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PI(3, 5)P2, phosphatidylinositol 3, 5-bisphosphate; PI, phosphatidylinositol; PI3P; PI3P, phosphatidylinositol 3-phosphate; PS, phosphatidylserine; PX, phox homology; SNARE; SNARE, soluble N-ethylmaleimide-sensitive factor attachment protein receptors; Vam7; Vmr1; Ybt1; Ycf1; lipid flipping