title: VAMP3/Syb and YKT6 are required for the fusion of constitutive secretory carriers with the plasma membrane.
abstract: The cellular machinery required for the fusion of constitutive secretory vesicles with the plasma membrane in metazoans remains poorly defined. To address this problem we have developed a powerful, quantitative assay for measuring secretion and used it in combination with combinatorial gene depletion studies in Drosophila cells. This has allowed us to identify at least three SNARE complexes mediating Golgi to PM transport (STX1, SNAP24/29 and Syb; STX1, SNAP24/29 and YKT6; STX4, SNAP24 and Syb). RNAi mediated depletion of YKT6 and VAMP3 in mammalian cells also blocks constitutive secretion suggesting that YKT6 has an evolutionarily conserved role in this process. The unexpected role of YKT6 in plasma membrane fusion may in part explain why RNAi and gene disruption studies have failed to produce the expected phenotypes in higher eukaryotes.
authors.affiliation: University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, United States of America.
authors.forename: David E
authors.identifier: 0000-0001-7954-0306
authors.initials: DE
authors.lastname: Gordon
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore.
authors.forename: Joanne
authors.initials: J
authors.lastname: Chia
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge, United Kingdom.
authors.forename: Kamburpola
authors.identifier: 0000-0002-7180-5469
authors.initials: K
authors.lastname: Jayawardena
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge, United Kingdom.
authors.forename: Robin
authors.identifier: 0000-0001-8608-4011
authors.initials: R
authors.lastname: Antrobus
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore.
authors.forename: Frederic
authors.initials: F
authors.lastname: Bard
authors.affiliation: Department of Biomedical Science & Centre for Membrane Interactions and Dynamics (CMIAD), The University of Sheffield, Western Bank, Sheffield, United Kingdom.
authors.forename: Andrew A
authors.identifier: 0000-0003-0144-7712
authors.initials: AA
authors.lastname: Peden
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008561:Membrane Fusion / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D050683:R-SNARE Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D050600:SNARE Proteins / Q000235:genetics* / Q000378:metabolism; D022622:Shiga Toxin 1 / Q000235:genetics / Q000378:metabolism; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins / Q000235:genetics / Q000378:metabolism; D051040:Vesicle-Associated Membrane Protein 3 / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D022622:Shiga Toxin 1; C494206:Snap24 protein, Drosophila; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; C092067:Syb protein, Drosophila; D051040:Vesicle-Associated Membrane Protein 3