Nature Reviews Molecular Cell Biology ( IF 81.3 ) Pub Date : 2022-09-27 , DOI: 10.1038/s41580-022-00531-5 Pakorn Kanchanawong 1, 2 , David A Calderwood 3, 4
The ability of animal cells to sense, adhere to and remodel their local extracellular matrix (ECM) is central to control of cell shape, mechanical responsiveness, motility and signalling, and hence to development, tissue formation, wound healing and the immune response. Cell–ECM interactions occur at various specialized, multi-protein adhesion complexes that serve to physically link the ECM to the cytoskeleton and the intracellular signalling apparatus. This occurs predominantly via clustered transmembrane receptors of the integrin family. Here we review how the interplay of mechanical forces, biochemical signalling and molecular self-organization determines the composition, organization, mechanosensitivity and dynamics of these adhesions. Progress in the identification of core multi-protein modules within the adhesions and characterization of rearrangements of their components in response to force, together with advanced imaging approaches, has improved understanding of adhesion maturation and turnover and the relationships between adhesion structures and functions. Perturbations of adhesion contribute to a broad range of diseases and to age-related dysfunction, thus an improved understanding of their molecular nature may facilitate therapeutic intervention in these conditions.
中文翻译:
整合素介导的细胞-ECM粘附的组织、动力学和机械调节
动物细胞感知、粘附和重塑其局部细胞外基质 (ECM) 的能力对于控制细胞形状、机械反应性、运动性和信号传导至关重要,从而对于发育、组织形成、伤口愈合和免疫反应至关重要。细胞-ECM 相互作用发生在各种专门的多蛋白粘附复合物上,这些复合物用于将 ECM 与细胞骨架和细胞内信号传导装置物理连接。这主要通过整合素家族的成簇跨膜受体发生。在这里,我们回顾机械力、生化信号和分子自组织的相互作用如何决定这些粘附的组成、组织、机械敏感性和动力学。在粘附中核心多蛋白模块的识别及其组件响应力的重排特征方面的进展,加上先进的成像方法,提高了对粘附成熟和周转以及粘附结构和功能之间关系的理解。粘附扰动会导致多种疾病和与年龄相关的功能障碍,因此更好地了解其分子性质可能有助于对这些疾病进行治疗干预。