Department of Biological Sciences , Ashoka University , Sonepat , Haryana 131029 , India.
Biochemistry. 2019 Nov 26;58(47):4677-4695. doi: 10.1021/acs.biochem.9b00442. Epub 2019 Aug 21.
Mechanotransduction from the extracellular matrix into the cell is primarily supervised by a transmembrane receptor, integrin, and a cytosolic protein, talin. Integrin binds ligands on the extracellular side, whereas talin couples integrin receptors to the actin cytoskeleton and later acts as a "force buffer". Talin and integrin together form a mechanosensitive signaling hub that regulates crucial cellular processes and pathways, including cell signaling and formation of focal adhesion complexes, which help cells to sense their mechano-environment and transduce the signal accordingly. Although both proteins function in tandem, most literature focuses on them individually. Here, we provide a focused review of the talin-integrin mechano-interactome network in light of its role in the process of mechanotransduction and its connection to diseases. While working under force, these proteins drive numerous biomolecular interactions and form adhesion complexes, which in turn control many physiological processes such as cell migration; thus, they are invariably associated with several diseases from leukocyte adhesion deficiency to cancer. Gaining insights into their role in the occurrence of these pathological disorders might lead us to establish treatment methods and therapeutic techniques.
细胞外基质向细胞内的力学转导主要由跨膜受体整合素和细胞质蛋白桩蛋白(talin)来监督。整合素结合细胞外配体,而桩蛋白将整合素受体与肌动蛋白细胞骨架偶联,随后充当“力缓冲器”。桩蛋白和整合素共同形成一个机械敏感的信号枢纽,调节包括细胞信号转导和粘着斑复合物形成在内的关键细胞过程和途径,有助于细胞感知其机械环境并相应地转导信号。尽管这两种蛋白协同作用,但大多数文献都单独研究它们。在本文中,我们结合机械转导过程以及与疾病的关联,聚焦于桩蛋白-整合素机械互作网络,对其进行综述。在受力时,这些蛋白驱动许多生物分子相互作用并形成粘着复合物,进而控制许多生理过程,如细胞迁移;因此,它们与从白细胞黏附缺陷到癌症等多种疾病都存在关联。深入了解它们在这些病理疾病发生过程中的作用,可能有助于我们建立治疗方法和治疗技术。