HOPS initiates vacuole docking by tethering membranes before trans-SNARE complex assembly

Vacuole homotypic fusion has been reconstituted with all purified components: vacuolar lipids, four soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, Sec17p, Sec18p, the Rab Ypt7p, and the hexameric homotypic fusion and vacuole protein sorting complex (HOPS). HO...

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Bibliographic Details
Published in:Molecular biology of the cell 2010-07, Vol.21 (13), p.2297-2305
Main Authors: Hickey, Christopher M, Wickner, William
Format: Article
Language:English
Subjects:
Cell Membrane - metabolism
Intracellular Membranes - metabolism
Liposomes - chemistry
Liposomes - metabolism
Membrane Fusion
Saccharomyces cerevisiae - cytology
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins - metabolism
Vacuoles - metabolism
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Summary:Vacuole homotypic fusion has been reconstituted with all purified components: vacuolar lipids, four soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, Sec17p, Sec18p, the Rab Ypt7p, and the hexameric homotypic fusion and vacuole protein sorting complex (HOPS). HOPS is a Rab-effector with direct affinity for SNAREs (presumably via its Sec1-Munc18 homologous subunit Vps33p) and for certain vacuolar lipids. Each of these pure vacuolar proteins was required for optimal proteoliposome clustering, raising the question of which was most directly involved. We now present model subreactions of clustering and fusion that reveal that HOPS is the direct agent of tethering. The Rab and vacuole lipids contribute to tethering by supporting the membrane association of HOPS. HOPS indirectly facilitates trans-SNARE complex formation by tethering membranes, because the synthetic liposome tethering factor polyethylene glycol can also stimulate trans-SNARE complex formation and fusion. SNAREs further stabilize the associations of HOPS-tethered membranes. HOPS then protects newly formed trans-SNARE complexes from disassembly by Sec17p/Sec18p.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.e10-01-0044