SNX9 couples actin assembly to Phosphoinositide signals and is required for membrane remodeling during endocytosis
SNX9 couples actin assembly to Phosphoinositide signals and is required for membrane remodeling during endocytosis
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DOI：
10.1016/j.devcel.2007.04.014
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发表时间：
2007-07-01
影响因子：
11.8
通讯作者：
Schmid, Sandra L.
中科院分区：
文献类型：
--
作者：
Yarar, Defne;Waterman-Storer, Clare M.;Schmid, Sandra L.
多种方式的内吞作用需要肌动蛋白依赖性的质膜重塑，然而，无论是连接这些过程的因素，也不了解其作用机制。分类连接蛋白SNX 9定位于网格蛋白包被的凹坑，在那里它与发动蛋白相互作用并在网格蛋白介导的内吞作用中起作用。在这里，我们证明，SNX 9也定位到肌动蛋白丰富的结构，涉及液相摄取，包括含有GPI锚定蛋白和背膜皱褶的管状膜。此外，我们表明，SNX 9是关键的背皱褶的形成和网格蛋白的独立，肌动蛋白依赖的液相内吞。在体外，SNX 9直接与N-WASP（Arp 2/3复合物激活剂）结合，并刺激N-WASP/Arp 2/3介导的肌动蛋白组装。SNX 9刺激的肌动蛋白聚合被含有PI 4，5 P2的脂质体大大增强，部分原因是PI 4，5 P2诱导的SNX 9寡聚化。这些结果表明，N-WASP依赖的肌动蛋白组件的空间和时间调节的机制，并牵连SNX 9在直接耦合肌动蛋白动力学的膜重塑在多种模式的内吞作用。
Multiple modes of endocytosis require actin-dependent remodeling of the plasma membrane; however, neither the factors linking these processes nor their mechanisms of action are understood. The sorting nexin, SNX9, localizes to clathrin-coated pits where it interacts with dynamin and functions in clathrin-mediated endocytosis. Here, we demonstrate that SNX9 also localizes to actin-rich structures implicated in fluid-phase uptake, including tubular membranes containing GPI-anchored proteins and dorsal membrane ruffles. Moreover, we show that SNX9 is critical for dorsal ruffle formation and for clathrin-independent, actin-dependent fluid-phase endocytosis. In vitro, SNX9 directly associates with N-WASP, an Arp2/3 complex activator, and stimulates N-WASP/Arp2/3-mediated actin assembly. SNX9-stimulated actin polymerization is greatly enhanced by PI4,5P2-containing liposomes, due in part to PI4,5P2-induced SNX9 oligomerization. These results suggest a mechanism for the spatial and temporal regulation of N-WASP-dependent actin assembly and implicate SNX9 in directly coupling actin dynamics to membrane remodeling during multiple modes of endocytosis.