The glycosyl phosphatidylinositol anchor of human T-cadherin binds lipoproteins.
T-cadherin (T-cad) is a Ca(2+)-dependent cell adhesion glycoprotein bound to the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor. T-cad expressed on vascular smooth muscle cells (SMC) binds lipoproteins on blot. To analyze the molecular basis for the interaction of T-cad with lipoproteins we expressed recombinant human T-cad in HEK293 cells. Whereas membrane-bound T-cad from SMC and T-cad transfected HEK293 cells bind lipoproteins, T-cadherin proteins cleaved from the cell surface by phosphatidylinositol-specific phospholipase C (PI-PLC) do not. The lipoprotein-binding function is also lacking both for a recombinant human T-cad expressed in HEK293 cells without the GPI signal sequence, and for a human T-cad form expressed in Escherichia coli that contains the signal sequence for GPI attachment but is not modified with a GPI. We conclude that the GPI moiety of T-cadherin is necessary and sufficient to mediate lipoprotein binding.
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Laboratory for Cardiovascular Research, Basel University Hospital, Basel, CH 4031, Switzerland. Thomas.niermann@unibas.ch
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D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D005347:Fibroblasts; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008168:Lung; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology; D009154:Mutation / Q000235:genetics; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D011485:Protein Binding; D016415:Sequence Alignment; D012995:Solubility; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
D015820:Cadherins; D017261:Glycosylphosphatidylinositols; C099972:H-cadherin; D008077:Lipoproteins, LDL; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase