Membrane fusion: five lipids, four SNAREs, three chaperones, two nucleotides, and a Rab, all dancing in a ring on yeast vacuoles.
Although fusion mechanisms are highly conserved in evolution and among organelles of the exocytic and endocytic pathways, yeast vacuole homotypic fusion offers unique technical advantages: excellent genetics, clear organelle cytology, in vitro colorimetric fusion assays, and reconstitution of fusion from all-pure components, including a Rab GTPase, HOPS (homotypic fusion and vacuole protein sorting complex), four SNAREs [soluble N-ethylmaleimide-sensitive factor (NSF) attachment receptors] that snare (bind) each other, SNARE-complex disassembly chaperones, and vacuolar lipids. Vacuole fusion studies offer paradigms of the interdependence of lipids and fusion proteins to assemble a fusion microdomain, distinct lipid functions, SNARE complex proofreading through the synergy between HOPS and the SNARE disassembly chaperones, and the role of each fusion protein in promoting radical bilayer restructuring for fusion without lysis.
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755-3844, USA. Bill.Wickner@Dartmouth.edu
William
W
Wickner
D011992:Endosomes / Q000378:metabolism; D050356:Lipid Metabolism; D008561:Membrane Fusion; D018832:Molecular Chaperones / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism*; D050600:SNARE Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism
D018832:Molecular Chaperones; D009711:Nucleotides; D050600:SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins; D020691:rab GTP-Binding Proteins