StarD7 behaves as a fusogenic protein in model and cell membrane bilayers

Biochim Biophys Acta. 2012 Mar;1818(3):425-33. doi: 10.1016/j.bbamem.2011.10.024. Epub 2011 Oct 28.

Abstract

StarD7 is a surface active protein, structurally related with the START lipid transport family. So, the present work was aimed at elucidating a potential mechanism of action for StarD7 that could be related to its interaction with a lipid-membrane interface. We applied an assay based on the fluorescence de-quenching of BD-HPC-labeled DMPC-DMPS 4:1 mol/mol SUVs (donor liposomes) induced by the dilution with non-labeled DMPC-DMPS 4:1 mol/mol LUVs (acceptor liposomes). Recombinant StarD7 accelerated the dilution of BD-HPC in a concentration-dependent manner. This result could have been explained by either a bilayer fusion or monomeric transport of the labeled lipid between donor and acceptor liposomes. Further experiments (fluorescence energy transfer between DPH-HPC/BD-HPC, liposome size distribution analysis by dynamic light scattering, and the multinuclear giant cell formation induced by recombinant StarD7) strongly indicated that bilayer fusion was the mechanism responsible for the StarD7-induced lipid dilution. The efficiency of lipid dilution was dependent on StarD7 electrostatic interactions with the lipid-water interface, as shown by the pH- and salt-induced modulation. Moreover, this process was favored by phosphatidylethanolamine which is known to stabilize non-lamellar phases considered as intermediary in the fusion process. Altogether these findings allow postulate StarD7 as a fusogenic protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism*
  • Giant Cells / chemistry
  • Giant Cells / metabolism
  • Humans
  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism*
  • Liposomes / chemistry
  • Liposomes / metabolism
  • Membrane Fusion / physiology*
  • Membrane Fusion Proteins / genetics
  • Membrane Fusion Proteins / metabolism*
  • Models, Biological*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Static Electricity

Substances

  • Carrier Proteins
  • Lipid Bilayers
  • Liposomes
  • Membrane Fusion Proteins
  • Recombinant Proteins
  • STARD7 protein, human