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      Nectin and Nectin-Like Molecules: Biology and Pathology

      a , b

      American Journal of Nephrology

      S. Karger AG

      Adherens Junction, Nectin, Necl, Rho, Rac, Cdc42, Rap

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          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.

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          Most cited references 94

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          Cell adhesion: the molecular basis of tissue architecture and morphogenesis.

           B Gumbiner (1996)
          A variety of cell adhesion mechanisms underlie the way that cells are organized in tissues. Stable cell interactions are needed to maintain the structural integrity of tissues, and dynamic changes in cell adhesion participate in the morphogenesis of developing tissues. Stable interactions actually require active adhesion mechanisms that are very similar to those involved in tissue dynamics. Adhesion mechanisms are highly regulated during tissue morphogenesis and are intimately related to the processes of cell motility and cell migration. In particular, the cadherins and the integrins have been implicated in the control of cell movement. Cadherin mediated cell compaction and cellular rearrangements may be analogous to integrin-mediated cell spreading and motility on the ECM. Regulation of cell adhesion can occur at several levels, including affinity modulation, clustering, and coordinated interactions with the actin cytoskeleton. Structural studies have begun to provide a picture of how the binding properties of adhesion receptors themselves might be regulated. However, regulation of tissue morphogenesis requires complex interactions between the adhesion receptors, the cytoskeleton, and networks of signaling pathways. Signals generated locally by the adhesion receptors themselves are involved in the regulation of cell adhesion. These regulatory pathways are also influenced by extrinsic signals arising from the classic growth factor receptors. Furthermore, signals generated locally be adhesion junctions can interact with classic signal transduction pathways to help control cell growth and differentiation. This coupling between physical adhesion and developmental signaling provides a mechanism to tightly integrate physical aspects of tissue morphogenesis with cell growth and differentiation, a coordination that is essential to achieve the intricate patterns of cells in tissues.
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            Transmembrane crosstalk between the extracellular matrix--cytoskeleton crosstalk.

            Integrin-mediated cell adhesions provide dynamic, bidirectional links between the extracellular matrix and the cytoskeleton. Besides having central roles in cell migration and morphogenesis, focal adhesions and related structures convey information across the cell membrane, to regulate extracellular-matrix assembly, cell proliferation, differentiation, and death. This review describes integrin functions, mechanosensors, molecular switches and signal-transduction pathways activated and integrated by adhesion, with a unifying theme being the importance of local physical forces.
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              A renaissance for SRC.


                Author and article information

                Am J Nephrol
                American Journal of Nephrology
                S. Karger AG
                October 2007
                06 September 2007
                : 27
                : 6
                : 590-604
                aDepartment of Molecular Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, and bOsaka University Graduate School of Medicine, Faculty of Medicine, Suita, Japan
                108103 Am J Nephrol 2007;27:590–604
                © 2007 S. Karger AG, Basel

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                Page count
                Figures: 5, Tables: 1, References: 124, Pages: 15
                Kidney and beyond – Review Article

                Cardiovascular Medicine, Nephrology

                Rac, Rho, Adherens Junction, Rap, Necl, Cdc42, Nectin


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