Bin2 is a membrane sculpting N-BAR protein that influences leucocyte podosomes, motility and phagocytosis.
Bin2 is a membrane sculpting N-BAR protein that influences leucocyte podosomes, motility and phagocytosis.
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DOI：
10.1371/journal.pone.0052401
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
McMahon HT
中科院分区：
文献类型：
--
作者：
Sánchez-Barrena MJ;Vallis Y;Clatworthy MR;Doherty GJ;Veprintsev DB;Evans PR;McMahon HT
细胞运动、粘附和吞噬作用由肌动蛋白和膜重塑过程控制。桥接整合子-2（Bin 2）也称为乳腺癌相关蛋白1（BRAP 1），是一种预测的含有N-BAR结构域的蛋白质，功能未知，在白细胞细胞中高度表达。在本研究中，我们解决了Bin 2 BAR结构域的结构，并在体外和体内研究其膜结合和弯曲性能。活细胞成像实验表明，Bin 2与质膜上富含肌动蛋白的结构相关，它通过其N-BAR结构域被靶向。Pull-down实验和免疫沉淀实验表明，Bin 2的C-末端结合了含有SH 3结构域的蛋白，如Endophilin A2和α-PIX。内源性蛋白质的siRNA导致细胞迁移减少，吞噬作用增加，并降低了podosome密度和动力学。相反，Bin 2的过表达导致吞噬作用降低，并增加了podosome密度和动力学。我们的结论是，Bin 2是一种膜雕刻蛋白，影响白细胞中的podosome形成，运动和吞噬作用。进一步了解这种蛋白质可能是了解白细胞在生理和病理条件下行为的关键。
Cell motility, adhesion and phagocytosis are controlled by actin and membrane remodelling processes. Bridging integrator-2 (Bin2) also called Breast cancer-associated protein 1 (BRAP1) is a predicted N-BAR domain containing protein with unknown function that is highly expressed in leucocytic cells. In the present study we solved the structure of Bin2 BAR domain and studied its membrane binding and bending properties in vitro and in vivo. Live-cell imaging experiments showed that Bin2 is associated with actin rich structures on the plasma membrane, where it was targeted through its N-BAR domain. Pull-down experiments and immunoprecipitations showed that Bin2 C-terminus bound SH3 domain containing proteins such as Endophilin A2 and α-PIX. siRNA of endogenous protein led to decreased cell migration, increased phagocytosis and reduced podosome density and dynamics. In contrast, overexpression of Bin2 led to decreased phagocytosis and increased podosome density and dynamics. We conclude that Bin2 is a membrane-sculpting protein that influences podosome formation, motility and phagocytosis in leucocytes. Further understanding of this protein may be key to understand the behaviour of leucocytes under physiological and pathological conditions.
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DOI：
10.1038/nrm3141
发表时间：
2011-06-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
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通讯作者：
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影响因子：
64.5
作者：
Boucrot E;Pick A;Çamdere G;Liska N;Evergren E;McMahon HT;Kozlov MM
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Kozlov MM
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
2.9
作者：
Casal, Eva;Federici, Luca;Laue, Ernest D.
通讯作者：
Laue, Ernest D.