This interaction has also been observed in the budding yeast Saccharomyces cerevisiae, in which the PSTPIP orthologue Bzz1p binds to the WASP orthologue Las17p ( Soulard et al., 2002). The best-characterised interaction is between F-BAR proteins and Wiskott-Aldrich syndrome protein (WASP) or neuronal-WASP (N-WASP), which are regulators of the actin-nucleating Arp2/3 complex ( Ho et al., 2004). The most commonly reported function of F-BAR proteins in mammalian cells is cytoskeletal organisation, often in close proximity to the plasma membrane. This structure generates a crescent-shaped molecule that has a family-specific radius of curvature. This consolidates a trend among membrane-bending proteins that contain BAR, N-BAR or F-BAR domains: the consequence of domain dimerization is the formation of a central six-helical bundle, from which two helices protrude on either side. The recent determination of the crystal structures of the F-BAR domains of mammalian FCHO2, FBP17 and CIP4 reveals that these domains are also structurally similar to BAR domains – characteristically, an elongated dimer formed by the antiparallel interaction of two α-helical coiled coils, each a three-helical bundle ( Henne et al., 2007 Shimada et al., 2007). Basic residues on the concave surface bind to negatively charged lipids, such as phosphatidylserine or phosphatidylinositol (4,5)-bisphosphate, through electrostatic interactions ( Gallop and McMahon, 2005). The crystal structures of the N-BAR and BAR domains have revealed that they are crescent-shaped dimers binding to highly curved membranes (outer radius ∼11-15 nm) via the concave surface of the protein ( Gallop and McMahon, 2005). This displacement induces membrane curvature, which is then stabilised by the BAR domain ( Weissenhorn, 2005 Gallop et al., 2006 Masuda et al., 2006). ![]() The hydrophobic face of the helix can insert into the hydrophobic phase of the membrane-lipid bilayer, displacing the phospholipids therein. Proteins of the N-terminal amphipathic helices BAR (N-BAR) family, a subset of the BAR-domain family, contain an N-terminal amphipathic helix that precedes the consensus BAR domain ( Weissenhorn, 2005 Gallop et al., 2006). Thus, the F-BAR domain is likely to act as a membrane-targeting module during endocytosis. This work was expanded by Itoh and colleagues and Tsujita and colleagues, who demonstrated that the F-BAR domain has an affinity for phospholipid-containing liposomes and induces membrane tubulation both in vivo and in vitro ( Itoh et al., 2005 Tsujita et al., 2006). A mutant form of FBP17 that is unable to bind to dynamin induces the formation of tubules that remain attached to the plasma membrane, leading the authors to conclude that the F-BAR domain acts in a manner similar to BAR domains and that an interaction with dynamin is required for endocytosis. The most striking evidence for the involvement of F-BAR proteins in endocytosis came from the observation by Kamioka and colleagues ( Kamioka et al., 2004), who reported that FBP17 induces tubular invaginations of the plasma membrane, and that the F-BAR domain is necessary and sufficient for this. members of the PACSIN/syndapin and CIP4 subfamilies) can bind to dynamin ( Itoh et al., 2005 Tsujita et al., 2006 Kessels and Qualmann, 2004), a GTPase that catalyses vesicle budding and scission of the lipid bilayer from intracellular membranes during clathrin-mediated endocytosis ( Shafer and Voss, 2004). The first link was the finding that the SH3 domain of some members of the F-BAR family (i.e. A large body of evidence implicates F-BAR proteins – including formin-binding protein 17 (FBP17, also known as FNBP1), CIP4, transducer of Cdc42-dependent actin assembly 1 (Toca1 also known as FNBP1L), proline-serine-threonine phosphatase-interacting proteins 1 and 2 (PSTPIP1 and PSTPIP2, respectively) – in endocytosis ( Kessels and Qualmann, 2004).
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