Shimono Yohei, Rikitake Yoshiyuki, Mandai Kenji, Mori Masahiro, Takai Yoshimi
Division of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 650-0017, Kobe, Japan.
Subcell Biochem. 2012;60:137-70. doi: 10.1007/978-94-007-4186-7_7.
The immunogroblin (Ig) superfamily proteins characterized by the presence of Ig-like domains are involved in various cellular functions. The properties of the Ig-like domains to form rod-like structures and to bind specifically to other proteins make them ideal for cell surface receptors and cell adhesion molecules (CAMs). Ig-CAMs, nectins in mammals and Echinoid in Drosophila, are crucial components of cadherin-based adherens junctions in the epithelium. Nectins form cell-cell adhesion by their trans-interactions and recruit cadherins to the nectin-initiated cell-cell adhesion site to establish adherens junctions. Thereafter junction adhesion molecules, occludin, and claudins, are recruited to the apical side of adherens junctions to establish tight junctions. The recruitment of these molecules by nectins is mediated both by the direct and indirect interactions of afadin with many proteins, such as catenins, and zonula occludens proteins, and by the nectin-induced reorganization of the actin cytoskeleton. Nectins contribute to the formation of both homotypic and heterotypic types of cell-cell junctions, such as synapses in the brain, contacts between pigment and non-pigment cell layers of the ciliary epithelium in the eye, Sertoli cell-spermatid junctions in the testis, and sensory cells and supporting cells in the sensory organs. In addition, cis- and trans-interactions of nectins with various cell surface proteins, such as integrins, growth factor receptors, and nectin-like molecules (Necls) play important roles in the regulation of many cellular functions, such as cell polarization, movement, proliferation, differentiation, survival, and cell sorting. Furthermore, the Ig-CAMs are implicated in many human diseases including viral infections, ectodermal dysplasia, cancers, and Alzheimer's disease.
以存在免疫球蛋白（Ig）样结构域为特征的免疫球蛋白超家族蛋白参与多种细胞功能。Ig样结构域形成杆状结构并与其他蛋白质特异性结合的特性使其成为细胞表面受体和细胞粘附分子（CAMs）的理想选择。Ig-CAMs，哺乳动物中的nectins和果蝇中的Echinoid，是上皮中基于钙粘蛋白的粘着连接的关键组成部分。Nectins通过其反式相互作用形成细胞间粘附，并将钙粘蛋白招募到由nectin启动的细胞间粘附位点以建立粘着连接。此后，连接粘附分子、闭合蛋白和紧密连接蛋白被招募到粘着连接的顶端以建立紧密连接。Nectins对这些分子的招募是由afadin与许多蛋白质（如连环蛋白和紧密连接蛋白）的直接和间接相互作用以及nectin诱导的肌动蛋白细胞骨架重排介导的。Nectins有助于同型和异型细胞间连接的形成，如大脑中的突触、眼睛睫状体上皮色素和非色素细胞层之间的接触、睾丸中的支持细胞-精子细胞连接以及感觉器官中的感觉细胞和支持细胞。此外，Nectins与各种细胞表面蛋白（如整合素、生长因子受体和nectin样分子（Necls））的顺式和反式相互作用在许多细胞功能的调节中起重要作用，如细胞极化、运动、增殖、分化、存活和细胞分选。此外，Ig-CAMs与许多人类疾病有关，包括病毒感染、外胚层发育不良、癌症和阿尔茨海默病。
