LMA1 binds to vacuoles at Sec18p (NSF), transfers upon ATP hydrolysis to a t-SNARE (Vam3p) complex, and is released during fusion.
Vacuole fusion requires Sec18p (NSF), Sec17p (alpha-SNAP), Ypt7p (GTP binding protein), Vam3p (t-SNARE), Nyv1p (v-SNARE), and LMA1 (low Mr activity 1, a heterodimer of thioredoxin and I(B)2). LMA1 requires Sec18p for saturable, high-affinity binding to vacuoles, and Sec18p "priming" ATPase requires both Sec17p and LMA1. Either the sec18-1 mutation and deletion of I(B)2, or deletion of both I(B)2 and p13 (an I(B)2 homolog) causes a striking synthetic vacuole fragmentation phenotype. Upon Sec18p ATP hydrolysis, LMA1 transfers to (and stabilizes) a Vam3p complex. LMA1 is released from vacuoles in a phosphatase-regulated reaction. This LMA1 cycle explains how priming by Sec18p is coupled to t-SNARE stabilization and to fusion.
Xu
Z
Z
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Sato
K
K
Wickner
W
W
D000251:Adenosine Triphosphatases; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006868:Hydrolysis; D008387:Marine Toxins; D008561:Membrane Fusion / Q000502:physiology*; D008565:Membrane Proteins; D052998:Microcystins; D008969:Molecular Sequence Data; D009154:Mutation; D010456:Peptides, Cyclic / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010750:Phosphoproteins; D011485:Protein Binding; D050765:Qa-SNARE Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology; D029701:Saccharomyces cerevisiae Proteins; D013879:Thioredoxins / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism*; D033921:Vesicular Transport Proteins
D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D006023:Glycoproteins; D008387:Marine Toxins; D008565:Membrane Proteins; D052998:Microcystins; D010456:Peptides, Cyclic; D010750:Phosphoproteins; D050765:Qa-SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins; C107706:VAM3 protein, S cerevisiae; D033921:Vesicular Transport Proteins; C018169:yeast proteinase B inhibitor; D013879:Thioredoxins; D000255:Adenosine Triphosphate; D010749:Phosphoprotein Phosphatases; D000251:Adenosine Triphosphatases; C064404:SEC18 protein, S cerevisiae; C057862:cyanoginosin LR