Bin-Amphiphysin-Rvs (BAR) domain proteins are crucial in regulating cell membrane curvature, a process necessary for endocytosis and cell motility. However, the mechanism that drives the oligomeric assembly of these proteins on membrane surfaces has remained largely unknown. Recently, a study published in Science Advances revealed the mechanism driving the oligomeric assembly of a BAR-domain-containing protein on membrane surfaces.
The researchers used fluorescence resonance energy transfer (FRET) to monitor the oligomeric assembly of F-BAR-containing GAS7 protein. Observing fluorescence emission indicated that GAS7 assembly on lipid membrane surfaces occurred rapidly, starting within seconds.
This process was enhanced by the presence of several proteins, including the Wiskott-Aldrich syndrome protein (WASP)/N-WASP, WISH, Nck, the activated small GTPase Cdc42, and a membrane-anchored phagocytic receptor.
The team further examined the role of WASP in GAS7 assembly and found that regulated GAS7 assembly was abolished by the WASP mutations both in vitro and during phagocytosis. This has implications for patients with Wiskott-Aldrich syndrome, which is associated with various immunological disorders and defective phagocytosis.
These findings provide opportunities for future studies on cellular shape formation and protein condensate studies. Since the WASP protein commonly binds to the BAR superfamily of proteins, the mechanism of assembly observed here is likely to function for other BAR proteins. These results have important implications for research on cellular shape formation and protein condensates.