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

ANGELETTI, SOFÍA; SANCHEZ, JULIETA MARÍA; CHAMLEY, LARRY W; GENTI- RAIMONDI, SUSANA DEL VALLE; PERILLO, MARÍA ANGELICA

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2012 vol. 1818 p. 425 - 433

0005-2736

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