T-CADHERIN AND SIGNAL-TRANSDUCING MOLECULES CO-LOCALIZE IN CAVEOLIN-RICH MEMBRANE DOMAINS OF VASCULAR SMOOTH-MUSCLE CELLS

Cadherins are a family of cellular adhesion proteins mediating homotyp ic cell-cell binding. In contrast to classical cadherins, T-cadherin d oes not possess the transmembrane and cytosolic domains known to be es sential for tight mechanical coupling of cells, and is instead attache d to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor. This study explores the hypothesis that T-cadherin might function as a signal-transducing protein. Membranes from human and rat vascular sm ooth muscle cells were fractionated using Triton X-100 solubilization and density gradient centrifugation techniques. We demonstrate that T- cadherin is enriched in a minor detergent-insoluble low-density membra ne domain and codistributes with caveolin, a marker of caveolae. This domain was enriched in other GPI-anchored proteins (CD-59, uPA recepto r) and signal-transducing molecules (G alpha s protein and Src-family kinases), but completely excluded cell-cell and cell-matrix adhesion m olecules (N-cadherin and beta 1-integrin). Coupling of T-cadherin with signalling molecules within caveolae might enable cellular signal tra nsduction. (C) 1998 Federation of European Biochemical Societies.