Phagocytosis is a cellular process for internalization of micron-sized large particles including pathogens. The Bin-Amphiphysin-Rvs167 (BAR) domain proteins, including the FCH-BAR (F-BAR) domain proteins, impose specific morphologies on lipid membranes. Most BAR domain proteins are thought to form membrane invaginations or protrusions by assembling into helical submicron-diameter filaments, such as on clathrin-coated pits, caveolae, and filopodia. However, the mechanism by which BAR domain proteins assemble into micron-scale phagocytic cups was unclear. Here, we show that the two-dimensional sheet-like assembly of Growth Arrest-Specific 7 (GAS7) plays a critical role in phagocytic cup formation in macrophages. GAS7 has the F-BAR domain that possesses unique hydrophilic loops for two-dimensional sheet formation on flat membranes. Super-resolution microscopy reveals the similar assemblies of GAS7 on phagocytic cups and liposomes. The mutations of the loops abolishes both the membrane localization of GAS7 and phagocytosis. Thus, the sheet-like assembly of GAS7 plays a significant role in phagocytosis.

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Background: Hibiscus sabdariffa L. or Roselle, is one of the most common flower plants cultivated worldwide. Traditionally, it is claimed to reduce weight and cholesterol level. The aim of this study was to evaluate the effects of anthocyanin-rich Roselle aqueous extract on the physical, biochemical and histological changes in obese-hypercholesterolaemic rat model.Methods: Thirty Sprague-Dawley male rats were divided into five groups (n=6 per group). Group 1 is normal control (NC) rat that was fed with normal diet. The remaining rats (Group 2-5) were fed with commercial high-fat diet (HFD) for 6 weeks to induce obese-hypercholesterolaemic (OH) rat. After induction, the OH rats were divided into 4 groups: OH-Untreated group, OH-ARTE; OH treated with 300 mg/kg Roselle aqueous (anthocyanin-rich) and 1% trifluoroacetic acid extract (ARTE), OH-Orlistat; OH treated with 37 mg/kg orlistat and OH-Atorvastatin; OH treated with 10 mg/kg atorvastatin. After the 3 weeks intervention period, all rats were sacrificed. Body mass index, lipid profile and liver enzymes were evaluated. The liver section was subjected to hematoxylin and eosin staining for histopathological evaluation.Results: This study showed that 3 weeks administration of ARTE significantly reduced BMI, improved levels of lipid profile and liver enzymes, and histopathological changes of liver when compared to OH-untreated rats. The results were also comparable to the standard drugs.Conclusions: This study suggested that Roselle extract constitutes an effective and safe alternate treatment for obesity and hyperlipidaemia.

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The higher-order assembly of Bin-amphiphysin-Rvs (BAR) domain proteins, including the FCH-BAR (F-BAR) domain proteins, into lattice on the membrane is essential for the formation of subcellular structures. However, the regulation of their ordered assembly has not been elucidated. Here, we show that the higher ordered assembly of growth-arrested specific 7 (GAS7), an F-BAR domain protein, is regulated by the multivalent scaffold proteins of Wiskott-Aldrich syndrome protein (WASP)/neural WASP, that commonly binds to the BAR domain superfamily proteins, together with WISH, Nck, the activated small guanosine triphosphatase Cdc42, and a membrane-anchored phagocytic receptor. The assembly kinetics by fluorescence resonance energy transfer monitoring indicated that the GAS7 assembly on liposomes started within seconds and was further increased by the presence of these proteins. The regulated GAS7 assembly was abolished by Wiskott-Aldrich syndrome mutations both in vitro and in cellular phagocytosis. Therefore, Cdc42 and the scaffold proteins that commonly bind to the BAR domain superfamily proteins promoted GAS7 assembly.