Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion

Nature. 2001 Feb 1;409(6820):581-8. doi: 10.1038/35054500.


SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) and Rab-GTPases, together with their cofactors, mediate the attachment step in the membrane fusion of vesicles. But how bilayer mixing--the subsequent core process of fusion--is catalysed remains unclear. Ca2+/calmodulin controls this terminal process in many intracellular fusion events. Here we identify V0, the membrane-integral sector of the vacuolar H+-ATPase, as a target of calmodulin on yeast vacuoles. Between docking and bilayer fusion, V0 sectors from opposing membranes form complexes. V0 trans-complex formation occurs downstream from trans-SNARE pairing, and depends on both the Rab-GTPase Ypt7 and calmodulin. The maintenance of existing complexes and completion of fusion are independent of trans-SNARE pairs. Reconstituted proteolipids form sealed channels, which can expand to form aqueous pores in a Ca2+/calmodulin-dependent fashion. V0 trans-complexes may therefore form a continuous, proteolipid-lined channel at the fusion site. We propose that radial expansion of such a protein pore may be a mechanism for intracellular membrane fusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calmodulin / metabolism*
  • Cell Membrane
  • Membrane Fusion*
  • Membrane Proteins / metabolism*
  • Protein Binding
  • Proteolipids / metabolism*
  • Proton Pumps / metabolism*
  • Proton-Translocating ATPases / metabolism*
  • SNARE Proteins
  • Vesicular Transport Proteins*
  • Yeasts


  • Calmodulin
  • Membrane Proteins
  • Proteolipids
  • Proton Pumps
  • SNARE Proteins
  • Vesicular Transport Proteins
  • Proton-Translocating ATPases