Nectin and Nectin-Like Molecules: Biology and Pathology

Abstract

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 αvβ3 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)α 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.

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

“…After sequestration of cadherins at the adherens junction, nectins continue to regulate cadherin function by (i) inhibiting the endocytosis of cadherin and (ii) affecting the conformation of cadherin extracellular domains to facilitate trans-interactions (Hoshino et al, 2005;Sato et al, 2006). Nectins also regulate cytoskeletal dynamics via F-actin binding proteins that interact directly with nectin [e.g., afadin, ␣-catenin, ␣-actinin, vinculin, annexin II and IQGAP Miyoshi and Takai, 2007)] (Fig. 1), and establishment of nectin-based adherens junctions required annexin II and IQGAP in MDCK cells (Katata et al, 2003;Yamada et al, 2005aYamada et al, , 2006a.…”

Identification of the amino-acid region involved in the intercellular interaction between the Na,K-ATPase β1 subunits

“…Homotypic trans-dimerization of E-cadherin is crucial for initiation of cellcell contact, whereas homotypic cis-dimerization is required for stabilization of adherens junctions (Wu et al, 2010). In addition to E-cadherin, another class of transmembrane proteins, nectins, have been recently identified as cell adhesion molecules in adherens junctions (Miyoshi and Takai, 2007;Takai et al, 2003). Nectins are thought to initiate cell-cell contact by forming hetero-trans dimers even before E-cadherin dimerization, which is then elaborated by nectin-facilitated cadherin recruitment.…”

Aberrations of a cell adhesion molecule CADM4 in renal clear cell carcinoma

“…In fact, in previous studies, it has been demonstrated that alterations of E-cadherin or integrins are frequently observed in RCCC. 5,6 We previously identified a tumor suppressor gene, CADM1/ TSLC1, in human nonsmall cell lung cancer (NSCLC). 7 The CADM1 is expressed in most epithelial tissues, while its expression is frequently lost in many tumors, including NSCLC or prostate cancer.…”