Drosophila Cip4/Toca-1 Integrates Membrane Trafficking and Actin Dynamics through WASP and SCAR/WAVE
Drosophila Cip4/Toca-1 Integrates Membrane Trafficking and Actin Dynamics through WASP and SCAR/WAVE
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DOI：
10.1016/j.cub.2009.07.058
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发表时间：
2009-09-15
期刊：
影响因子：
9.2
通讯作者：
Bogdan, Sven
中科院分区：
文献类型：
--
作者：
Fricke, Robert;Gohl, Christina;Bogdan, Sven
背景：发育过程与整合肌动蛋白细胞骨架动态重组和膜动力学的信号事件密切相关。结果：我们对果蝇F-bar蛋白Cip4/Toca1(CDC42-相互作用蛋白4/依赖于CDC42的肌动蛋白组件转导蛋白1)进行了功能分析。Cip4能够与WASP和SCAR/WAVE形成复合体，并招募促进肌动蛋白成核的因子内陷细胞膜和内吞小泡。这些囊泡基于肌动蛋白-彗星-尾巴的运动不仅依赖于WASP，而且在很大程度上取决于波函数。在体内，cip4功能的丧失会导致多个翼毛。当动力蛋白抑制后，囊泡断裂受到影响时，也观察到类似的表型。基因剂量实验表明，Cip4和WAVE在功能上相互作用，限制翼毛的形成。进一步的抢救实验证实，Cip4在体内能够通过WAVE和WASP发挥作用。生化和功能数据支持CDC42作用于Cip4上游的模型，该模型不仅招募WASP，而且通过Abi招募SCAR/WAVE来控制翅膀上动力蛋白依赖的细胞极化。结论：CIP4通过WASP和WAVE整合了膜运输和肌动蛋白动力学。首先，Cip4通过将动力素募集到新生囊泡的颈部来促进膜内陷并触发囊泡破裂。第二，Cip4招募WASP和WAVE蛋白来诱导肌动蛋白聚合，支持囊泡断裂，为囊泡运动提供力量。
Background: Developmental processes are intimately tied to signaling events that integrate the dynamic reorganization of the actin cytoskeleton and membrane dynamics. The F-BAR-domain-containing proteins are prime candidates to couple actin dynamics and membrane trafficking in different morphogenetic processes.Results: Here, we present the functional analysis of the Drosophila F-BAR protein Cip4/Toca1 (Cdc42-interacting protein 4/transducer of Cdc42-dependent actin assembly 1). Cip4 is able to form a complex with WASP and SCAR/WAVE and recruits both actin-nucleation-promoting factors to invaginating membranes and endocytic vesicles. Actin-comet-tail-based movement of these vesicles depends not only on WASP but largely on WAVE function. In vivo, loss of cip4 function causes multiple wing hairs. A similar phenotype is observed when vesicle scission is affected after Dynamin suppression. Gene dosage experiments show that Cip4 and WAVE functionally interact to restrict wing hair formation. Further rescue experiments confirm that Cip4 is able to act through WAVE and WASP in vivo. Biochemical and functional data support a model in which Cdc42 acts upstream of Cip4 and recruits not only WASP but also SCAR/WAVE via Abi to control Dynamin-dependent cell polarization in the wing.Conclusion: Cip4 integrates membrane trafficking and actin dynamics through WASP and WAVE. First, Cip4 promotes membrane invaginations and triggers the vesicle scission by recruiting Dynamin to the neck of nascent vesicles. Second, Cip4 recruits WASP and WAVE proteins to induce actin polymerization, supporting vesicle scission and providing the force for vesicle movement.