Department of Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China; Department of Clinical Pharmacy, The Second Hospital of Shandong University, Jinan 250033, China.
Department of Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
Int J Biol Macromol. 2019 Jun 15;131:378-386. doi: 10.1016/j.ijbiomac.2019.03.041. Epub 2019 Mar 6.
The desmosome is a member of intercellular junctions that named 'anchoring junction', which contributes to the integrity and homeostasis of tissue structure and function of multicellular living organisms. As an important component of the desmosome and the most widely distributed isoform of desmocollins (DSCs), desmocollin2 (DSC2) has been demonstrated to be essential for the unity of epithelial cells, and served as a vital regulator in signaling processes such as epithelial morphogenesis, differentiation, wound healing, cell apoptosis, migration, and proliferation. Recent studies suggested that the aberrant expression or disruption of DSC2 might lead to some disorders, including heart disorders, certain cancers, and some other human diseases. The distinctions in expression and regulation mechanisms of DSC2 in different human diseases provided a potential target for diagnosis and individualized treatment. Further research is required to certify the signaling capacity of DSC2 and to shed light on the down-stream consequences of the signaling for us to understand the new area of DSC2 biology and the development of certain diseases. This review summarizes the molecular structure and dynamics of desmosome and DSC2, the relationship between the disruption or aberrant expression of DSC2 and human diseases and related molecular mechanisms, as well as the possible prospects.
桥粒是细胞连接的一种，又称“锚定连接”，对多细胞生物组织的结构和功能的完整性和动态平衡有重要作用。桥粒中的黏附分子包括桥粒芯糖蛋白和桥粒胶蛋白，其中桥粒胶蛋白分为两类：desmogleins（DSGs）和 desmocollins（DSCs）。黏合斑蛋白（vinculin）是桥粒斑的主要连接蛋白，桥粒相关蛋白（plakophilins）和 plakoglobin 等蛋白通过桥粒斑与中间纤维相连。桥粒通过 desmosomal cadherins 与相邻细胞黏附，桥粒相关蛋白和桥粒胶蛋白通过 desmosomal plakoglobin 与肌动蛋白细胞骨架相连。作为桥粒的重要组成部分和 DSCs 中分布最广泛的亚型，桥粒胶蛋白 2（DSC2）对于上皮细胞的完整性至关重要，在信号转导过程中发挥着重要的调节作用，如上皮形态发生、分化、伤口愈合、细胞凋亡、迁移和增殖等。最近的研究表明，DSC2 的异常表达或缺失可能导致一些疾病，包括心脏疾病、某些癌症和其他一些人类疾病。DSC2 在不同人类疾病中的表达和调控机制的差异为疾病的诊断和个体化治疗提供了潜在的靶点。进一步的研究需要证实 DSC2 的信号转导能力，并阐明信号转导的下游后果，以帮助我们了解 DSC2 生物学的新领域和某些疾病的发展。本文综述了桥粒和 DSC2 的分子结构和动力学、DSC2 的缺失或异常表达与人类疾病的关系及其相关分子机制，并对可能的前景进行了展望。
