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肌营养不良蛋白相关蛋白复合体的进化与发育功能:超越肌肉特异性细胞黏附复合体的概念

Evolution and developmental functions of the dystrophin-associated protein complex: beyond the idea of a muscle-specific cell adhesion complex.

作者信息

Mirouse Vincent

机构信息

Institute of Genetics, Reproduction and Development (iGReD), Université Clermont Auvergne-UMR CNRS 6293-INSERM U1103, Faculté de Médecine, Clermont-Ferrand, France.

出版信息

Front Cell Dev Biol. 2023 Jun 13;11:1182524. doi: 10.3389/fcell.2023.1182524. eCollection 2023.

Abstract

The Dystrophin-Associated Protein Complex (DAPC) is a well-defined and evolutionarily conserved complex in animals. DAPC interacts with the F-actin cytoskeleton via dystrophin, and with the extracellular matrix via the membrane protein dystroglycan. Probably for historical reasons that have linked its discovery to muscular dystrophies, DAPC function is often described as limited to muscle integrity maintenance by providing mechanical robustness, which implies strong cell-extracellular matrix adhesion properties. In this review, phylogenetic and functional data from different vertebrate and invertebrate models will be analyzed and compared to explore the molecular and cellular functions of DAPC, with a specific focus on dystrophin. These data reveals that the evolution paths of DAPC and muscle cells are not intrinsically linked and that many features of dystrophin protein domains have not been identified yet. DAPC adhesive properties also are discussed by reviewing the available evidence of common key features of adhesion complexes, such as complex clustering, force transmission, mechanosensitivity and mechanotransduction. Finally, the review highlights DAPC developmental roles in tissue morphogenesis and basement membrane (BM) assembly that may indicate adhesion-independent functions.

摘要

肌营养不良蛋白相关蛋白复合体(DAPC)是动物体内一种明确且在进化上保守的复合体。DAPC通过肌营养不良蛋白与F-肌动蛋白细胞骨架相互作用,并通过膜蛋白肌聚糖与细胞外基质相互作用。可能由于其发现与肌肉营养不良症相关的历史原因,DAPC的功能通常被描述为通过提供机械稳定性来维持肌肉完整性,这意味着具有强大的细胞-细胞外基质黏附特性。在本综述中,将分析和比较来自不同脊椎动物和无脊椎动物模型的系统发育和功能数据,以探索DAPC的分子和细胞功能,特别关注肌营养不良蛋白。这些数据表明,DAPC和肌肉细胞的进化路径并非内在相关,并且肌营养不良蛋白结构域的许多特征尚未被识别。通过回顾黏附复合体共同关键特征的现有证据,如复合体聚集、力传递、机械敏感性和机械转导,也对DAPC的黏附特性进行了讨论。最后,综述强调了DAPC在组织形态发生和基底膜(BM)组装中的发育作用,这些作用可能表明其具有不依赖黏附的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7161/10293626/7f76cfea7b05/fcell-11-1182524-g001.jpg

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