Miyoshi Jun, Takai Yoshimi
Department of Molecular Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
Am J Nephrol. 2007;27(6):590-604. doi: 10.1159/000108103. Epub 2007 Sep 6.
Nectins and nectin-like molecules (Necls) are structurally related transmembrane proteins primarily involved in cell adhesion. Nectins and afadin, the adaptor or anchoring protein, stabilize the epithelium and endothelium and establish apical-basal polarity of epithelial cells, independently or in cooperation with other cell adhesion molecules. Necls facilitate cell-cell communication implicated in cell movement and proliferation, immune responses, and cancer cell phenotypes. Necls interact with nectins and specific ligands at cell-cell contacts, whereas Necls associate with integrin alpha v beta 3 and growth factor receptors on the same cell surface. Besides their roles in cell adhesion, nectins regulate the activities of Rho family small G proteins which play critical roles in maintaining the apical junctions of epithelial cells through reorganization of the actin cytoskeleton. Since mice lacking the Rho GDP-dissociation inhibitor (GDI)alpha show massive proteinuria and degeneration of renal epithelial cells, nectins and other cell adhesion molecules may play roles in the structural and functional aspects of renal diseases. Here we summarize our knowledge of nectins and Necls and discuss cell adhesion biology in the kidney.
NECTIN蛋白和NECTIN样分子(Necls)是结构相关的跨膜蛋白,主要参与细胞黏附。NECTIN蛋白和衔接蛋白或锚定蛋白afadin可稳定上皮细胞和内皮细胞,并独立或与其他细胞黏附分子协同建立上皮细胞的顶-基极性。Necls促进与细胞运动和增殖、免疫反应及癌细胞表型相关的细胞间通讯。Necls在细胞间接触处与NECTIN蛋白和特定配体相互作用,而Necls在同一细胞表面与整合素αvβ3和生长因子受体相关联。除了在细胞黏附方面的作用外,NECTIN蛋白还调节Rho家族小G蛋白的活性,这些小G蛋白通过肌动蛋白细胞骨架的重组在维持上皮细胞顶端连接中起关键作用。由于缺乏Rho GDP解离抑制剂(GDI)α的小鼠表现出大量蛋白尿和肾上皮细胞变性,NECTIN蛋白和其他细胞黏附分子可能在肾脏疾病的结构和功能方面发挥作用。在此,我们总结了我们对NECTIN蛋白和Necls的认识,并讨论了肾脏中的细胞黏附生物学。