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

• Published in: Biochimica et biophysica acta 2012-03, Vol.1818 (3), p.425-433
• Main Authors: Angeletti, Sofía, Sanchez, Julieta M., Chamley, Larry W., Genti-Raimondi, Susana, Perillo, María A.
• Format: Article
• Language: English
• Subjects: Bilayer fusion; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Cell Membrane - chemistry; Cell Membrane - metabolism; Dynamic light scattering; FRET; 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; StarD7; Static Electricity; Steady state fluorescence de-quenching; Trophoblast syncytialisation
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2011.10.024

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. ► Finding of a biological activity for this protein which so far had no known function. ► Description of a StarD7 activity not demonstrated (not tested?) for structurally related proteins. ► Demonstration of StarD7 participation in trophoblast differentiation through membrane fusion. ► The biophysical perspective accounted for the complexity of fluorophore dilution experiments.