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Shiro Suetsugu - One of the best experts on this subject based on the ideXlab platform.
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membrane re modelling by BAR Domain superfamily proteins via molecular and non molecular factors
Biochemical Society Transactions, 2018Co-Authors: Tamako Nishimura, Nobuhiro Morone, Shiro SuetsuguAbstract:Lipid membranes are structural components of cell surfaces and intracellular organelles. Alterations in lipid membrane shape are accompanied by numerous cellular functions, including endocytosis, intracellular transport, and cell migration. Proteins containing Bin-Amphiphysin-Rvs (BAR) Domains (BAR proteins) are unique, because their structures correspond to the membrane curvature, that is, the shape of the lipid membrane. BAR proteins present at high concentration determine the shape of the membrane, because BAR Domain oligomers function as scaffolds that mould the membrane. BAR proteins co-operate with various molecular and non-molecular factors. The molecular factors include cytoskeletal proteins such as the regulators of actin filaments and the membrane scission protein dynamin. Lipid composition, including saturated or unsaturated fatty acid tails of phospholipids, also affects the ability of BAR proteins to mould the membrane. Non-molecular factors include the external physical forces applied to the membrane, such as tension and friction. In this mini-review, we will discuss how the BAR proteins orchestrate membrane dynamics together with various molecular and non-molecular factors.
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Salt Bridge Formation between the I-BAR Domain and Lipids Increases Lipid Density and Membrane Curvature
Scientific Reports, 2017Co-Authors: Kazuhiro Takemura, Kyoko Hanawa-suetsugu, Shiro Suetsugu, Akio KitaoAbstract:The BAR Domain superfamily proteins sense or induce curvature in membranes. The inverse-BAR Domain (I-BAR) is a BAR Domain that forms a straight “zeppelin-shaped” dimer. The mechanisms by which IRSp53 I-BAR binds to and deforms a lipid membrane are investigated here by all-atom molecular dynamics simulation (MD), binding energy analysis, and the effects of mutation experiments on filopodia on HeLa cells. I-BAR adopts a curved structure when crystallized, but adopts a flatter shape in MD. The binding of I-BAR to membrane was stabilized by ~30 salt bridges, consistent with experiments showing that point mutations of the interface residues have little effect on the binding affinity whereas multiple mutations have considerable effect. Salt bridge formation increases the local density of lipids and deforms the membrane into a concave shape. In addition, the point mutations that break key intra-molecular salt bridges within I-BAR reduce the binding affinity; this was confirmed by expressing these mutants in HeLa cells and observing their effects. The results indicate that the stiffness of I-BAR is important for membrane deformation, although I-BAR does not act as a completely rigid template.
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Yeast Ivy1p Is a Putative I-BAR-Domain Protein with pH-sensitive Filament Forming Ability in vitro
Cell Structure and Function, 2015Co-Authors: Yuzuru Itoh, Kyoko Hanawa-suetsugu, Kazuki Kida, Shiro SuetsuguAbstract:Bin-Amphiphysin-Rvs161/167 (BAR) Domains mold lipid bilayer membranes into tubules, by forming a spiral polymer on the membrane. Most BAR Domains are thought to be involved in forming membrane invaginations through their concave membrane binding surfaces, whereas some members have convex membrane binding surfaces, and thereby mold membranes into protrusions. The BAR Domains with a convex surface form a subtype called the inverse BAR (I-BAR) Domain or IRSp53-MIM-homology Domain (IMD). Although the mammalian I-BAR Domains have been studied, those from other organisms remain elusive. Here, we found putative I-BAR Domains in Fungi and animal-like unicellular organisms. The fungal protein containing the putative I-BAR-Domain is known as Ivy1p in yeast, and is reportedly localized in the vacuole. The phylogenetic analysis of the I-BAR Domains revealed that the fungal I-BAR-Domain containing proteins comprise a distinct group from those containing IRSp53 or MIM. Importantly, Ivy1p formed a polymer with a diameter of approximately 20 nm in vitro, without a lipid membrane. The filaments were formed at neutral pH, but disassembled when pH was reverted to basic. Moreover, Ivy1p and the I-BAR Domain expressed in mammalian HeLa cells was localized at a vacuole-like structure as filaments as revealed by super-resolved microscopy. These data indicate the pH-sensitive polymer forming ability and the functional conservation of Ivy1p in eukaryotic cells.
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possible regulation of caveolar endocytosis and flattening by phosphorylation of f BAR Domain protein pacsin2 syndapin ii
BioArchitecture, 2015Co-Authors: Yosuke Senju, Shiro SuetsuguAbstract:Caveolae are flask-shaped invaginations of the plasma membrane. The BAR Domain proteins form crescent-shaped dimers, and their oligomeric filaments are considered to form spirals at the necks of invaginations, such as clathrin-coated pits and caveolae. PACSIN2/Syndapin II is one of the BAR Domain-containing proteins, and is localized at the necks of caveolae. PACSIN2 is thought to function in the scission and stabilization of caveolae, through binding to dynamin-2 and EHD2, respectively. These two functions are considered to be switched by PACSIN2 phosphorylation by protein kinase C (PKC) upon hypotonic stress and sheer stress. The phosphorylation decreases the membrane binding affinity of PACSIN2, leading to its removal from caveolae. The removal of the putative oligomeric spiral of PACSIN2 from caveolar membrane invaginations could lead to the deformation of caveolae. Indeed, PACSIN2 removal from caveolae is accompanied by the recruitment of dynamin-2, suggesting that the removal provides space for the function of dynamin-2. Otherwise, the removal of PACSIN2 decreases the stability of caveolae, which could result in the flattening of caveolae. In contrast, an increase in the amount of EHD2 restored caveolar stability. Therefore, PACSIN2 at caveolae stabilizes caveolae, but its removal by phosphorylation could induce both caveolar endocytosis and flattening.
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The BAR Domain Superfamily Proteins from Subcellular Structures to Human Diseases
Membranes, 2012Co-Authors: Fatemeh Safari, Shiro SuetsuguAbstract:Eukaryotic cells have complicated membrane systems. The outermost plasma membrane contains various substructures, such as invaginations and protrusions, which are involved in endocytosis and cell migration. Moreover, the intracellular membrane compartments, such as autophagosomes and endosomes, are essential for cellular viability. The Bin-Amphiphysin-Rvs167 (BAR) Domain superfamily proteins are important players in membrane remodeling through their structurally determined membrane binding surfaces. A variety of BAR Domain superfamily proteins exist, and each family member appears to be involved in the formation of certain subcellular structures or intracellular membrane compartments. Most of the BAR Domain superfamily proteins contain SH3 Domains, which bind to the membrane scission molecule, dynamin, as well as the actin regulatory WASP/WAVE proteins and several signal transduction molecules, providing possible links between the membrane and the cytoskeleton or other machineries. In this review, we summarize the current information about each BAR superfamily protein with an SH3 Domain(s). The involvement of BAR Domain superfamily proteins in various diseases is also discussed.
Volker Haucke - One of the best experts on this subject based on the ideXlab platform.
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A Coincidence Detection Mechanism Controls PX-BAR Domain-Mediated Endocytic Membrane Remodeling via an Allosteric Structural Switch
Developmental Cell, 2017Co-Authors: Andreja Vujičić Žagar, Fabian Gerth, Martin Lehmann, Dymtro Puchkov, Oxana Krylova, Christian Freund, Leonardo Scapozza, Oscar Vadas, Volker HauckeAbstract:Clathrin-mediated endocytosis occurs by bending and remodeling of the membrane underneath the coat. Bin-amphiphysin-rvs (BAR) Domain proteins are crucial for endocytic membrane remodeling, but how their activity is spatiotemporally controlled is largely unknown. We demonstrate that the membrane remodeling activity of sorting nexin 9 (SNX9), a late-acting endocytic PX-BAR Domain protein required for constriction of U-shaped endocytic intermediates, is controlled by an allosteric structural switch involving coincident detection of the clathrin adaptor AP2 and phosphatidylinositol-3,4-bisphosphate (PI(3,4)P2) at endocytic sites. Structural, biochemical, and cell biological data show that SNX9 is autoinhibited in solution. Binding to PI(3,4)P2 via its PX-BAR Domain, and concomitant association with AP2 via sequences in the linker region, releases SNX9 autoinhibitory contacts to enable membrane constriction. Our results reveal a mechanism for restricting the latent membrane remodeling activity of BAR Domain proteins to allow spatiotemporal coupling of membrane constriction to the progression of the endocytic pathway.
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lipid mediated px BAR Domain recruitment couples local membrane constriction to endocytic vesicle fission
Nature Communications, 2017Co-Authors: Volker Haucke, Martin Lehmann, Johannes Schoneberg, Alexander Ullrich, York Posor, Gregor Lichtner, Jan SchmoranzerAbstract:Clathrin-mediated endocytosis (CME) involves membrane-associated scaffolds of the bin-amphiphysin-rvs (BAR) Domain protein family as well as the GTPase dynamin, and is accompanied and perhaps triggered by changes in local lipid composition. How protein recruitment, scaffold assembly and membrane deformation is spatiotemporally controlled and coupled to fission is poorly understood. We show by computational modelling and super-resolution imaging that phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] synthesis within the clathrin-coated area of endocytic intermediates triggers selective recruitment of the PX-BAR Domain protein SNX9, as a result of complex interactions of endocytic proteins competing for phospholipids. The specific architecture induces positioning of SNX9 at the invagination neck where its self-assembly regulates membrane constriction, thereby providing a template for dynamin fission. These data explain how lipid conversion at endocytic pits couples local membrane constriction to fission. Our work demonstrates how computational modelling and super-resolution imaging can be combined to unravel function and mechanisms of complex cellular processes.
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BAR Domain Scaffolds in Dynamin-Mediated Membrane Fission
Cell, 2014Co-Authors: Oliver Daumke, Aurélien Roux, Volker HauckeAbstract:Biological membranes undergo constant remodeling by membrane fission and fusion to change their shape and to exchange material between subcellular compartments. During clathrin-mediated endocytosis, the dynamic assembly and disassembly of protein scaffolds comprising members of the bin-amphiphysin-rvs (BAR) Domain protein superfamily constrain the membrane into distinct shapes as the pathway progresses toward fission by the GTPase dynamin. In this Review, we discuss how BAR Domain protein assembly and disassembly are controlled in space and time and which structural and biochemical features allow the tight regulation of their shape and function to enable dynamin-mediated membrane fission.
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membrane shaping by the bin amphiphysin rvs BAR Domain protein superfamily
Cellular and Molecular Life Sciences, 2011Co-Authors: Volker Haucke, Yijian RaoAbstract:BAR Domain superfamily proteins have emerged as central regulators of dynamic membrane remodeling, thereby playing important roles in a wide variety of cellular processes, such as organelle biogenesis, cell division, cell migration, secretion, and endocytosis. Here, we review the mechanistic and structural basis for the membrane curvature-sensing and deforming properties of BAR Domain superfamily proteins. Moreover, we summarize the present state of knowledge with respect to their regulation by autoinhibitory mechanisms or posttranslational modifications, and their interactions with other proteins, in particular with GTPases, and with membrane lipids. We postulate that BAR superfamily proteins act as membrane-deforming scaffolds that spatiotemporally orchestrate membrane remodeling.
Yosuke Senju - One of the best experts on this subject based on the ideXlab platform.
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possible regulation of caveolar endocytosis and flattening by phosphorylation of f BAR Domain protein pacsin2 syndapin ii
BioArchitecture, 2015Co-Authors: Yosuke Senju, Shiro SuetsuguAbstract:Caveolae are flask-shaped invaginations of the plasma membrane. The BAR Domain proteins form crescent-shaped dimers, and their oligomeric filaments are considered to form spirals at the necks of invaginations, such as clathrin-coated pits and caveolae. PACSIN2/Syndapin II is one of the BAR Domain-containing proteins, and is localized at the necks of caveolae. PACSIN2 is thought to function in the scission and stabilization of caveolae, through binding to dynamin-2 and EHD2, respectively. These two functions are considered to be switched by PACSIN2 phosphorylation by protein kinase C (PKC) upon hypotonic stress and sheer stress. The phosphorylation decreases the membrane binding affinity of PACSIN2, leading to its removal from caveolae. The removal of the putative oligomeric spiral of PACSIN2 from caveolar membrane invaginations could lead to the deformation of caveolae. Indeed, PACSIN2 removal from caveolae is accompanied by the recruitment of dynamin-2, suggesting that the removal provides space for the function of dynamin-2. Otherwise, the removal of PACSIN2 decreases the stability of caveolae, which could result in the flattening of caveolae. In contrast, an increase in the amount of EHD2 restored caveolar stability. Therefore, PACSIN2 at caveolae stabilizes caveolae, but its removal by phosphorylation could induce both caveolar endocytosis and flattening.
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Subcellular membrane curvature mediated by the BAR Domain superfamily proteins.
Seminars in Cell & Developmental Biology, 2009Co-Authors: Shiro Suetsugu, Kiminori Toyooka, Yosuke SenjuAbstract:The Bin-Amphiphysin-Rvs167 (BAR) Domain superfamily consists of proteins containing the BAR Domain, the extended FCH (EFC)/FCH-BAR (F-BAR) Domain, or the IRSp53-MIM homology Domain (IMD)/inverse BAR (I-BAR) Domain. These Domains bind membranes through electrostatic interactions between the negative charges of the membranes and the positive charges on the structural surface of homo-dimeric BAR Domain superfamily members. Some BAR superfamily members have membrane-penetrating insertion loops, which also contribute to the membrane binding by the proteins. The membrane-binding surface of each BAR Domain superfamily member has its own unique curvature that governs or senses the curvature of the membrane for BAR-Domain binding. The wide range of BAR-Domain surface curvatures correlates with the various invaginations and protrusions of cells. Therefore, each BAR Domain superfamily member may generate and recognize the curvature of the membrane of each subcellular structure, such as clathrin-coated pits or filopodia. The BAR Domain superfamily proteins may regulate their own catalytic activity or that of their binding proteins, depending on the membrane curvature of their corresponding subcellular structures.
Anton Arkhipov - One of the best experts on this subject based on the ideXlab platform.
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Computer Simulation of Membrane Tubulation by EFC F-BAR Domain Lattices
Biophysical Journal, 2012Co-Authors: Klaus Schulten, Ying Yin, Anton ArkhipovAbstract:Cells are dynamically sculpted into many types of compartments by cellular membranes, in some cases with the help of BAR Domain proteins. BAR Domain proteins act under in vitro conditions are found to induce formation of tubules. We have seen in coarse-grained molecular dynamics simulation stretching over 100 microseconds how a flat membrane is curved into a tube when F-BAR Domain proteins are arranged on the membrane surface as a regular lattice of parallel rows. The simulations could also characterize the membrane bending properties of F-BAR Domains in different lattice arrangements, showing membrane curvatures with radii ranging from 25 to 100 nm.Lastly, the simulations reveal two key structural features of F-BAR Domain that facilitate efficient binding to membranes and membrane curving: (1) Curving is promoted by close contact between phosphoserine lipid head groups and clusters of cationic residues along the membrane facing surface of F-BAR Domains, namely lysine and arginine residues 30, 33, 110, 113, 114, and 139, 140, 146, 150, respectively. (2) Within the 100 ns of contact, the F-BAR Domain hinge region, through a 20 degree rotation of the helix moment of inertia, establishes a close contact between protein and membrane. (1) and (2) result in membrane bending on a microsecond-to-millisecond time scale.
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Simulation of Membrane Sculpting by EFC F-BAR Domain Lattices
Biophysical Journal, 2010Co-Authors: Ying Yin, Anton ArkhipovAbstract:Cells, during cellular morphogenesis, are dynamically sculpted into different compartments by membranes with the help of proteins. The BAR Domain is one of the conserved protein Domains that is involved in shaping cellular membranes in vivo, and is observed to induce tubule formation from liposomes in vitro. Previous simulations showed that certain lattice arrangements of N-BAR Domains shape membranes into tubules (Yin, Arkhipov, and Schulten, 2009). Here we show, by means of several microsecond coarse-grained simulations of F-BAR Domains in different lattice configurations on POPC/POPS membranes, that extended-FCH (EFC) F-BAR Domains shape membrane in a fashion similar to what has been seen in N-BAR simulations. The membrane bending property of several F-BAR Domain lattice arrangements is characterized, showing that different lattice configurations induce a range of membrane curvatures. A highly detailed view of the dynamic membrane sculpting process by F-BAR Domain lattices on a microsecond timescale is obtained.Yin, Y., Arkhipov, A., and Schulten, K. (2009). Simulations of membrane tubulation by lattices of amphiphysin N-BAR Domains. Structure17(6), 882-92.
Johannes Schoneberg - One of the best experts on this subject based on the ideXlab platform.
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lipid mediated px BAR Domain recruitment couples local membrane constriction to endocytic vesicle fission
Nature Communications, 2017Co-Authors: Volker Haucke, Martin Lehmann, Johannes Schoneberg, Alexander Ullrich, York Posor, Gregor Lichtner, Jan SchmoranzerAbstract:Clathrin-mediated endocytosis (CME) involves membrane-associated scaffolds of the bin-amphiphysin-rvs (BAR) Domain protein family as well as the GTPase dynamin, and is accompanied and perhaps triggered by changes in local lipid composition. How protein recruitment, scaffold assembly and membrane deformation is spatiotemporally controlled and coupled to fission is poorly understood. We show by computational modelling and super-resolution imaging that phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] synthesis within the clathrin-coated area of endocytic intermediates triggers selective recruitment of the PX-BAR Domain protein SNX9, as a result of complex interactions of endocytic proteins competing for phospholipids. The specific architecture induces positioning of SNX9 at the invagination neck where its self-assembly regulates membrane constriction, thereby providing a template for dynamin fission. These data explain how lipid conversion at endocytic pits couples local membrane constriction to fission. Our work demonstrates how computational modelling and super-resolution imaging can be combined to unravel function and mechanisms of complex cellular processes.
