The BAR domain superfamily: membrane-molding macromolecules

Abstract

Membrane-shaping proteins of the BAR domain superfamily are determinants of organelle biogenesis, membrane trafficking, cell division, and cell migration. An upsurge of research now reveals new principles of BAR domain-mediated membrane remodeling, enhancing our understanding of membrane curvature-mediated information processing.

Figure 1. Cellular Structures and BAR Domain Proteins

(A) Plasma membrane tubules in cells demonstrating the shape-based scaffolding properties of the F-BAR structure. Cells expressing GFP-FBP17 visualized by fluorescence (top left), by transmission electron microscopy (TEM; bottom left), and by cryo-EM-derived single particle reconstruction of an F-BAR-coated tubule generated in vitro (bottom and top right) (Shimada et al., 2007, Frost et al., 2008). (B) I-BAR domains of the missing-in-metastasis (MIM) protein localize to the plasma membrane and filopodia (Mattila et al., 2007; originally published in JCB 176, 953–964). (C) TEM of a Drosophila neuromuscular synapse engineered to overexpress syndapin in muscle, revealing an expansion of the subsynaptic reticulum (reprinted with permission from Kumar et al., 2009). (D) (Left) Immunofluorescence of a skeletal muscle frozen section demonstrating muscle amphiphysin-2 (white) along transverse bands flanking the Z-line. (Right) Frozen section showing immunogold-labeled muscle amphiphysin-2 revealing its concentration on a T-tubule (Butler et al., 1997; originally published in JCB 137,1355–1367). (E) TEM of a transformed BHK21 cell cut perpendicular to the substratum to demonstrate the presence of tubular membrane invaginations in a podosome (Ochoa et al., 2000; originally published in JCB 150, 377–389). (F1) Negative staining of liposomes incubated with amphiphysin-1 and a clathrin coat fraction (reprinted with permission from Macmillan Publishers Ltd: Takei et al., Nat. Cell Biol. 1, 33–39, 1999; copyright 1999). (F2) TEM of the synapse of a neuron deficient in dynamin-1, showing clathrin-coated endocytic pits originating from a plasma membrane tubular invagination ~30 nm in diameter (from Ferguson et al., 2007, Science 316, 570–574; reprinted with permission from AAAS). (F3) TEM showing an endocytic coated pit with a narrow-neck connection to the surface (reprinted from Exp. Cell Res., Goldenthal et al., 1984, 152, pp. 558–564, copyright 1984; with permission from Elsevier). (F4) GFP-GRAF1 endocytic tubules turn over in ~10 min (Lundmark et al., 2008). (F5) TEM of immunogold-labeled glycosyl phosphatidylinositol (GPI)-anchored proteins internalized via a putative clathrin- and dynamin-independent invagination (reprinted with permission from Macmillan Publishers Ltd: Mayor and Pagano, Nat. Rev. Mol. Cell Biol. 8, 603–612, 2007; copyright 2007). The invagination is like that induced by GRAF1 (Lundmark et al., 2008).

Figure 2. Do BAR Domain Proteins Link the Contractile Ring to the Cleavage Furrow?

(A) Shown is a cartoon of a dividing fission yeast cell with representations of where the F-BAR domains of Cdc15 (green) may localize in relation to the actomyosin contractile ring (red). (B) Cells expressing mCFP-Wsp1 (red) and Cdc15-mYFP (green), showing that Cdc15p colocalizes with precursors of the contractile ring and with fully formed contractile rings at various stages of constriction (Wu et al., 2006; originally published in JCB 174, 391–402). (C) TEM of cleavage furrow invagination in fission yeast (reproduced with permission from Kanbe, 1989). The diameter of the edge of the invagination ranges from 50 to 80 nm, within the range of known BAR and F-BAR structures. Regions where F-BAR domains of Cdc15 may localize in relation to the contractile ring are shown. Bar: 2000 nm (B), 100 nm (C).