The Vtc proteins in vacuole fusion: coupling NSF activity to V(0) trans-complex formation

EMBO J. 2002 Feb 1;21(3):259-69. doi: 10.1093/emboj/21.3.259.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases*
  • Carrier Proteins / physiology*
  • Fungal Proteins / physiology*
  • Glycoproteins / physiology
  • Membrane Fusion / physiology*
  • Membrane Proteins / physiology*
  • Molecular Chaperones / physiology*
  • SNARE Proteins
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins*
  • Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
  • Thioredoxins
  • Vacuoles / physiology
  • Vesicular Transport Proteins*


  • Carrier Proteins
  • Fungal Proteins
  • Glycoproteins
  • Membrane Proteins
  • Molecular Chaperones
  • SNARE Proteins
  • Saccharomyces cerevisiae Proteins
  • Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
  • VTC1 protein, S cerevisiae
  • Vesicular Transport Proteins
  • yeast proteinase B inhibitor
  • Thioredoxins
  • Adenosine Triphosphatases
  • SEC18 protein, S cerevisiae