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Cbl-associated protein regulates assembly and function of two tension-sensing structures in Drosophila

机译:Cbl相关蛋白调节果蝇中两个张力感应结构的装配和功能

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摘要

Cbl-associated protein (CAP) localizes to focal adhesions and associates with numerous cytoskeletal proteins; however, its physiological roles remain unknown. Here, we demonstrate that Drosophila CAP regulates the organization of two actin-rich structures in Drosophila: muscle attachment sites (MASs), which connect somatic muscles to the body wall; and scolopale cells, which form an integral component of the fly chordotonal organs and mediate mechanosensation. Drosophila CAP mutants exhibit aberrant junctional invaginations and perturbation of the cytoskeletal organization at the MAS. CAP depletion also results in collapse of scolopale cells within chordotonal organs, leading to deficits in larval vibration sensation and adult hearing. We investigate the roles of different CAP protein domains in its recruitment to, and function at, various muscle subcellular compartments. Depletion of the CAP-interacting protein Vinculin results in a marked reduction in CAP levels at MASs, and vinculin mutants partially phenocopy Drosophila CAP mutants. These results show that CAP regulates junctional membrane and cytoskeletal organization at the membrane-cytoskeletal interface of stretch-sensitive structures, and they implicate integrin signaling through a CAP/Vinculin protein complex in stretch-sensitive organ assembly and function.
机译:Cbl相关蛋白(CAP)定位于粘着斑并与许多细胞骨架蛋白相关。然而,其生理作用仍然未知。在这里,我们证明果蝇CAP调节果蝇中两个富含肌动蛋白的结构的组织:肌肉附着位点(MAS),它将体肌连接到体壁;以及扇形细胞,它们构成了蝇形软骨器官的组成部分并介导了机械感觉。果蝇CAP突变体在MAS表现出异常的交界内陷和细胞骨架组织的扰动。 CAP消耗还会导致软骨细胞内的扇形细胞崩溃,导致幼虫的振动感觉和成人听力下降。我们调查了不同的CAP蛋白域在其募集到各种肌肉亚细胞区室并在其中起作用的作用。 CAP相互作用蛋白Vinculin的耗竭会导致MASs的CAP水平显着降低,而纽蛋白突变体部分表现为果蝇CAP突变体。这些结果表明,CAP调节牵张敏感结构的膜细胞骨架界面处的连接膜和细胞骨架组织,并且它们通过牵张敏感器官组装和功能中的CAP / Vinulin蛋白复合物暗示整联蛋白信号传导。

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