Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Development. 2013 Feb 1;140(3):627-38. doi: 10.1242/dev.085100.
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.
Cbl 相关蛋白（CAP）定位于粘着斑并与许多细胞骨架蛋白相关联；然而，其生理功能仍然未知。在这里，我们证明果蝇 CAP 调节果蝇中两种富含肌动蛋白的结构的组织：肌肉附着位点（MASs），将体壁肌肉连接到身体壁；和感觉棍细胞，它们是蝇类听毛器官的一个组成部分，并介导机械感觉。果蝇 CAP 突变体表现出异常的连接内陷和 MAS 处细胞骨架组织的紊乱。CAP 耗竭也导致听毛器官内感觉棍细胞的崩溃，导致幼虫振动感觉和成虫听力缺陷。我们研究了不同 CAP 蛋白结构域在其募集和功能方面在各种肌肉亚细胞区室中的作用。CAP 相互作用蛋白 Vinculin 的耗竭导致 MAS 处 CAP 水平的显著降低，并且 vinculin 突变体部分模拟果蝇 CAP 突变体。这些结果表明 CAP 调节伸展敏感结构的膜-细胞骨架界面处的连接膜和细胞骨架组织，并且它们表明通过 CAP/Vinculin 蛋白复合物的整联蛋白信号传导在伸展敏感器官组装和功能中。
