Glycosyl phosphatidylinositol--anchored T-cadherin mediates calcium-dependent, homophilic cell adhesion.
Cadherins are a family of cell adhesion molecules that exhibit calcium-dependent, homophilic binding. Their function depends on both an HisAlaVal sequence in the first extracellular domain, EC1, and the interaction of a conserved cytoplasmic region with intracellular proteins. T-cadherin is an unusual member of the cadherin family that lacks the HisAlaVal motif and is anchored to the membrane through a glycosyl phosphatidylinositol moiety (Ranscht, B., and M. T. Dours-Zimmermann. 1991. Neuron. 7:391-402). To assay the function of T-cadherin in cell adhesion, we have transfected T-cadherin cDNA into CHO cells. Two proteins, mature T-cadherin and the uncleaved T-cadherin precursor, were produced from T-cadherin cDNA. The T-cadherin proteins differed from classical cadherins in several aspects. First, the uncleaved T-cadherin precursor was expressed, together with mature T-cadherin, on the surface of the transfected cells. Second, in the absence of calcium, T-cadherin was more resistant to proteolytic cleavage than other cadherins. Lastly, in contrast to classical cadherins, T-cadherin was not concentrated into cell-cell contacts between transfected cells in monolayer cultures. In cellular aggregation assays, T-cadherin induced calcium-dependent, homophilic adhesion which was abolished by treatment of T-cadherin-transfected cells with phosphatidylinositol-specific phospholipase C. These results demonstrate that T-cadherin is a functional cadherin that differs in several properties from classical cadherins. The function of T-cadherin in homophilic cell recognition implies that the mechanism of T-cadherin-induced adhesion is distinct from that of classical cadherins.
Vestal
D J
DJ
La Jolla Cancer Research Foundation, National Cancer Institute, California 92037.
Ranscht
B
B
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000737:chemistry; D017124:Conserved Sequence; D006224:Cricetinae; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D008969:Molecular Sequence Data; D015739:Nocodazole / Q000494:pharmacology; D011498:Protein Precursors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014357:Trypsin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000494:pharmacology
D015820:Cadherins; D017261:Glycosylphosphatidylinositols; C099972:H-cadherin; D011498:Protein Precursors; D015638:Cytochalasin D; D010738:Type C Phospholipases; D014357:Trypsin; D015739:Nocodazole; D002118:Calcium