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 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 (G alpha s protein and Src-family kinases), but completely excluded cell-cell and cell-matrix adhesion molecules (N-cadherin and beta1-integrin). Coupling of T-cadherin with signalling molecules within caveolae might enable cellular signal transduction.
Philippova
M P
MP
Laboratory of Molecular Endocrinology, Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia.
Bochkov
V N
VN
Stambolsky
D V
DV
Tkachuk
V A
VA
Resink
T J
TJ
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D051242:Caveolin 1; D022461:Caveolins; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
C495540:CAV1 protein, human; D015820:Cadherins; C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins; C099972:H-cadherin; D008565:Membrane Proteins