title: The Vtc proteins in vacuole fusion: coupling NSF activity to V(0) trans-complex formation.
abstract: The fusion of cellular membranes comprises several steps; membrane attachment requires priming of SNAREs and tethering factors by Sec18p/NSF (N-ethylmaleimide sensitive factor) and LMA1. This leads to trans-SNARE pairing, i.e. formation of SNARE complexes between apposed membranes. The yeast vacuole system has revealed two subsequent molecular events: trans-complex formation of V-ATPase proteolipid sectors (V(0)) and release of LMA1 from the membrane. We have now identified a hetero-oligomeric membrane integral complex of vacuolar transporter chaperone (Vtc) proteins integrating these events. The Vtc complex associates with the R-SNARE Nyv1p and with V(0). Subunits Vtc1p and Vtc4p control the initial steps of fusion. They are required for Sec18p/NSF activity in SNARE priming, membrane binding of LMA1 and V(0) trans-complex formation. In contrast, subunit Vtc3p is required for the latest step, LMA1 release, but dispensible for all preceding steps, including V(0) trans-complex formation. This suggests that Vtc3p might act close to or at fusion pore opening. We propose that Vtc proteins may couple ATP-dependent NSF activity to a subset of V(0) sectors in order to activate them for V(0) trans-complex formation and/or control fusion pore opening.
authors.affiliation: Friedrich-Miescher-Laboratorium der Max-Planck-Gesellschaft, Spemannstrasse 37-39, D-72076 Tübingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Müller
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Bayer
authors.forename: Christopher
authors.initials: C
authors.lastname: Peters
authors.forename: Jens S
authors.initials: JS
authors.lastname: Andersen
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.forename: Andreas
authors.initials: A
authors.lastname: Mayer
mesh_terms: D000251:Adenosine Triphosphatases; D002352:Carrier Proteins / Q000502:physiology*; D005656:Fungal Proteins / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology; D008561:Membrane Fusion / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D018832:Molecular Chaperones / Q000502:physiology*; D050600:SNARE Proteins; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D013879:Thioredoxins; D014617:Vacuoles / Q000502:physiology; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D005656:Fungal Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D050600:SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; C499587:VTC1 protein, S cerevisiae; D033921:Vesicular Transport Proteins; C018169:yeast proteinase B inhibitor; D013879:Thioredoxins; D000251:Adenosine Triphosphatases; C064404:SEC18 protein, S cerevisiae