Glycosyl Phosphatidylinositol-Anchored T-Cadherin Mediates Calcium-Dependent, Homophilic Cell Adhesion

• Published in: The Journal of cell biology Vol. 119; no. 2; pp. 451 - 461
• Main Authors: Vestal, Deborah J., Ranscht, Barbara
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.10.1992; The Rockefeller University Press
• Subjects: Aggregation; Amino Acid Sequence; Animals; Antiserum; Biological and medical sciences; Cadherins; Cadherins - drug effects; Cadherins - genetics; Cadherins - metabolism; Calcium - pharmacology; Cell adhesion; Cell Adhesion - drug effects; Cell Adhesion - physiology; Cell adhesion molecules; Cell aggregates; Cell interactions, adhesion; Cell lines; Cell Membrane - chemistry; Cells; Cellular biology; CHO Cells; Conserved Sequence; Cricetinae; Cytochalasin D - pharmacology; Cytoskeleton - drug effects; Cytoskeleton - physiology; Fundamental and applied biological sciences. Psychology; Glycosylphosphatidylinositols - metabolism; Molecular and cellular biology; Molecular Sequence Data; Neurons; Nocodazole - pharmacology; Protein Precursors - drug effects; Protein Precursors - genetics; Protein Precursors - metabolism; Transfection; Trypsin - pharmacology; Type C Phospholipases - pharmacology; Morphogenesis; Regulation(control); Sensitivity; Calcium; Ions; Adhesion; Recognition
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.119.2.451

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 contracts 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.