Formation of membrane ridges and scallops by the F-BAR protein Nervous Wreck.
Formation of membrane ridges and scallops by the F-BAR protein Nervous Wreck.
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DOI：
10.1091/mbc.e13-05-0271
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发表时间：
2013-08
影响因子：
3.3
通讯作者：
Rodal AA
中科院分区：
文献类型：
--
作者：
Becalska AN;Kelley CF;Berciu C;Stanishneva-Konovalova TB;Fu X;Wang S;Sokolova OS;Nicastro D;Rodal AA
NWK是一种神经元F-bar/SH3蛋白，它使用新月形F-bar结构域的锯齿形组装将膜变形为正弯曲的脊状结构。相邻脊间的膜形成一个负弯曲的扇贝，该扇贝可以被细胞骨架放大成细胞突起。真核细胞的定义是广泛的细胞内区域化，这需要动态的膜重塑。FER/Cip4同源-Bin/两面体/RVS(F-bar)结构域蛋白形成新月形二聚体，可以将膜弯曲成确定的几何形状和脂质组成的芽和小管。然而，这些蛋白质在体外和体内表现出无法解释的膜变形活性和功能的广泛多样性。我们发现神经元蛋白NWK的F-bar结构域具有一种新的高阶结构和膜变形活性，这使其有别于先前描述的F-bar蛋白。NWK的F-bar结构域在体外组装成之字形，在膜上形成脊状和周期性的扇贝。这种活性依赖于F-bar二聚体末端的结构决定因素以及膜与F-bar凹面的静电相互作用。在细胞中，NWK诱导的扇贝可以通过细胞骨架的力量扩展，在质膜上产生突起。我们的结果定义了一种新的F-bar膜变形活性，并阐明了正弯曲的F-bar结构域可以产生不同的膜曲率的分子机制。这些发现扩大了F-bar结构域介导的膜变形的谱系，并表明独特的高阶组装模式可以定义这些蛋白质如何塑造膜。
Nwk is a neuronal F-BAR/SH3 protein that deforms membranes into positively curved ridges using a novel zigzag assembly of the crescent-shaped F-BAR domain. Membrane between adjacent ridges forms a negatively curved scallop that can be amplified by the cytoskeleton into cellular protrusions. Eukaryotic cells are defined by extensive intracellular compartmentalization, which requires dynamic membrane remodeling. FER/Cip4 homology-Bin/amphiphysin/Rvs (F-BAR) domain family proteins form crescent-shaped dimers, which can bend membranes into buds and tubules of defined geometry and lipid composition. However, these proteins exhibit an unexplained wide diversity of membrane-deforming activities in vitro and functions in vivo. We find that the F-BAR domain of the neuronal protein Nervous Wreck (Nwk) has a novel higher-order structure and membrane-deforming activity that distinguishes it from previously described F-BAR proteins. The Nwk F-BAR domain assembles into zigzags, creating ridges and periodic scallops on membranes in vitro. This activity depends on structural determinants at the tips of the F-BAR dimer and on electrostatic interactions of the membrane with the F-BAR concave surface. In cells, Nwk-induced scallops can be extended by cytoskeletal forces to produce protrusions at the plasma membrane. Our results define a new F-BAR membrane-deforming activity and illustrate a molecular mechanism by which positively curved F-BAR domains can produce a variety of membrane curvatures. These findings expand the repertoire of F-BAR domain mediated membrane deformation and suggest that unique modes of higher-order assembly can define how these proteins sculpt the membrane.