T-cadherin and signal-transducing molecules co-localize in caveolin-rich membrane domains of vascular smooth muscle cells

• Published in: FEBS letters 1998-06, Vol.429 (2), p.207-210
• Main Authors: Philippova, M.P, Bochkov, V.N, Stambolsky, D.V, Tkachuk, V.A, Resink, T.J
• Format: Article
• Language: English
• Subjects: Animals; Cadherin; Cadherins - metabolism; Caveolin 1; Caveolins; Cell Fractionation; Cell Membrane - metabolism; Cells, Cultured; GPI, glycosylphosphatidylinositol; Humans; LDL, low-density lipoprotein; Lipoprotein; mAB, monoclonal antibody; Membrane Proteins - metabolism; Muscle, Smooth, Vascular - metabolism; pAB, polyclonal antibody; Rats; Signal Transduction; uPA, urokinase-type plasminogen activator; Vascular smooth muscle cell; VSMC, vascular smooth muscle cells
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(98)00598-5

Cadherins are a family of cellular adhesion proteins mediating homotypic cell-cell binding. In contrast to classical cadherins, T-cadherin does not possess the transmembrane and cytosolic domains known to be essential for tight mechanical coupling of cells, and is instead attached 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 smooth 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 membrane domain and co-distributes with caveolin, a marker of caveolae. This domain was enriched in other GPI-anchored proteins (CD-59, uPA receptor) and signal-transducing molecules (Gαs protein and Src-family kinases), but completely excluded cell-cell and cell-matrix adhesion molecules (N-cadherin and β1-integrin). Coupling of T-cadherin with signalling molecules within caveolae might enable cellular signal transduction.