LDL binds to surface-expressed human T-cadherin in transfected HEK293 cells and influences homophilic adhesive interactions.
T-cadherin (T-cad) is an unusual glycosylphosphatidylinositol-anchored member of the cadherin family of cell adhesion molecules. Binding of low density lipoproteins (LDLs) to T-cad can be demonstrated on Western blots of smooth muscle cell lysates, membranes and purified proteins. Using HEK293 cells transfected with human T-cad cDNA (T-cad+), we have investigated the adhesion properties of expressed mature and precursor proteins and examined the postulate that LDL represents a physiologically relevant ligand for T-cad. T-cad+ exhibits an increased Ca(2+)-dependent aggregation (vs. control) that was reduced by selective proteolytic cleavage of precursor T-cad and abolished after either proteolytic or phosphatidylinositol-specific phospholipase C (PI-PLC) cleavage of both mature and precursor proteins, indicating that both proteins function in intercellular adhesion. T-cad+ exhibited a significantly increased specific cell surface-binding of [(125)I]-LDL that was sensitive to PI-PLC pre-treatment of cells. Ca(2+)-dependent intercellular adhesion of T-cad+ was significantly inhibited by LDL. Our results support the suggestion that LDL is a physiologically relevant ligand for T-cad.
Resink
T J
TJ
Laboratory for Cardiovascular Research, Department of Research, Basel University Hospital, CH 4031, Basel, Switzerland. therese-j.resink@unibas.ch
Kuzmenko
Y S
YS
Kern
F
F
Stambolsky
D
D
Bochkov
V N
VN
Tkachuk
V A
VA
Erne
P
P
Niermann
T
T
D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015151:Immunoblotting; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D011485:Protein Binding; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
D015820:Cadherins; C099972:H-cadherin; D008077:Lipoproteins, LDL; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D002118:Calcium