Nervous wreck and Cdc42 cooperate to regulate endocytic actin assembly during synaptic growth.
Nervous wreck and Cdc42 cooperate to regulate endocytic actin assembly during synaptic growth.
复制标题
神经残骸和CDC42在突触生长过程中合作调节内吞肌动蛋白组件。
DOI：
10.1523/jneurosci.2304-08.2008
复制
发表时间：
2008-08-13
影响因子：
5.3
通讯作者：
Littleton, J. Troy
中科院分区：
文献类型：
--
作者：
Rodal, Avital A.;Motola-Barnes, Rebecca N.;Littleton, J. Troy
突触形态的调节依赖于激活的生长信号受体的内吞作用，但调节这种膜运输事件的机制尚不清楚。由WASp（Wiskott-Aldrich综合征蛋白）和Arp 2/3（肌动蛋白相关蛋白2/3）复合物介导的肌动蛋白聚合在胞吞作用的多个阶段产生力。F-BAR/SH 3结构域蛋白通过协调膜变形和WASP依赖的肌动蛋白聚合在这一过程中发挥关键作用。然而，目前还不知道其他WASp配体，如小GTdR Cdc 42，如何与F-BAR/SH 3蛋白协调，以调节肌动蛋白在膜上的聚合。Nervous Wreck（Nwk）是一种保守的神经元F-BAR/SH 3蛋白，定位于果蝇幼虫神经肌肉接头（NMJ）的活动周区，并且是通过BMP信号传导调节突触生长所必需的。在这里，我们表明，Nwk与内吞蛋白dynamin和Dap 160相互作用，并与Cdc 42一起发挥作用，以促进WASP介导的肌动蛋白聚合在体外和调节突触生长在体内。Cdc 42的功能与Rab 11依赖的再循环内体相关，我们发现Rab 11与Nwk在NMJ共定位。两者合计，我们的研究结果表明，生长因子信号激活的突触生长控制在内体隔室通过协调Nwk和Cdc 42依赖的肌动蛋白组装。
Regulation of synaptic morphology depends on endocytosis of activated growth signal receptors, but the mechanisms regulating this membrane trafficking event are unclear. Actin polymerization mediated by WASp (Wiskott-Aldrich Syndrome Protein) and the Arp2/3 (Actin related protein 2/3) complex generates forces at multiple stages of endocytosis. F-BAR/SH3 domain proteins play key roles in this process by coordinating membrane deformation with WASp-dependent actin polymerization. However, it is not known how other WASp ligands, such as the small GTPase Cdc42, coordinate with F-BAR/SH3 proteins to regulate actin polymerization at membranes. Nervous Wreck (Nwk) is a conserved neuronal F-BAR/SH3 protein that localizes to periactive zones at the Drosophila larval neuromuscular junction (NMJ) and is required for regulation of synaptic growth via BMP signaling. Here we show that Nwk interacts with the endocytic proteins dynamin and Dap160 and functions together with Cdc42 to promote WASp-mediated actin polymerization in vitro and to regulate synaptic growth in vivo. Cdc42 function is associated with Rab11-dependent recycling endosomes, and we show that Rab11 co-localizes with Nwk at the NMJ. Taken together, our results suggest that synaptic growth activated by growth factor signaling is controlled at an endosomal compartment via coordinated Nwk and Cdc42-dependent actin assembly.