Phosphoinositides and membrane curvature switch the mode of actin polymerization via selective recruitment of toca-1 and Snx9
Phosphoinositides and membrane curvature switch the mode of actin polymerization via selective recruitment of toca-1 and Snx9
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DOI：
10.1073/pnas.1305286110
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发表时间：
2013-04-30
影响因子：
11.1
通讯作者：
Kirschner，Marc W.
中科院分区：
文献类型：
--
作者：
Gallop，Jennifer L.;Walrant，Astrid;Kirschner，Marc W.
膜-胞质界面是肌动蛋白聚合的主要控制位点。在这个界面，磷酸肌醇作为第二信使招募膜结合蛋白。我们发现，弯曲的膜，而不是平坦的，可以使用磷脂酰肌醇3-磷酸[PI（3）P]沿着与磷脂酰肌醇4，5-二磷酸[PI（4，5）P2]刺激肌动蛋白聚合。在这种情况下，肌动蛋白聚合需要小G T细胞周期分裂42（Cdc 42）、成核促进因子神经Wiskott-Aldrich综合征蛋白（N-WASP）和肌动蛋白成核剂肌动蛋白相关蛋白（阿普）2/3复合物。在含有PI（4，5）P2作为唯一磷酸肌醇的脂质体中，肌动蛋白聚合需要Cdc 42活化-1（toca-1）的换能器。在磷脂酰肌醇3-磷酸的存在下，聚合是更有效的和独立的toca-1。在这些条件下，分选连接蛋白9（Snx 9）可以作为一个特定的衔接子，取代toca-1动员神经Wiskott-Aldrich综合征蛋白和Arp 2/3复合物。磷酸肌醇和肌动蛋白聚合的适配器特异性从膜上的这种开关具有不同类型的肌动蛋白结构是如何在精确的时间和位置在细胞中产生的影响。
The membrane–cytosol interface is the major locus of control of actin polymerization. At this interface, phosphoinositides act as second messengers to recruit membrane-binding proteins. We show that curved membranes, but not flat ones, can use phosphatidylinositol 3-phosphate [PI(3)P] along with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] to stimulate actin polymerization. In this case, actin polymerization requires the small GTPase cell cycle division 42 (Cdc42), the nucleation-promoting factor neural Wiskott–Aldrich syndrome protein (N-WASP) and the actin nucleator the actin-related protein (Arp) 2/3 complex. In liposomes containing PI(4,5)P2 as the sole phosphoinositide, actin polymerization requires transducer of Cdc42 activation-1 (toca-1). In the presence of phosphatidylinositol 3-phosphate, polymerization is both more efficient and independent of toca-1. Under these conditions, sorting nexin 9 (Snx9) can be implicated as a specific adaptor that replaces toca-1 to mobilize neural Wiskott–Aldrich syndrome protein and the Arp2/3 complex. This switch in phosphoinositide and adaptor specificity for actin polymerization from membranes has implications for how different types of actin structures are generated at precise times and locations in the cell.