LDL binds to surface‐expressed human T‐cadherin in transfected HEK293 cells and influences homophilic adhesive interactions

Abstract

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.z 1999 Federation of European Biochemical Societies.

T-Cadherin-Mediated Cell Growth Regulation Involves G2 Phase Arrest and Requires p21CIP1/WAF1 Expression

“…In contrast to the classical cadherins (45,49), T-cadherin is not concentrated in regions of cell-cell contact (1), but it can induce calcium-dependent homophilic aggregation in CHO cells (69) and in HEK293 cells (54). Under standard in vitro culture conditions, T-cadherin-transfected C6 cells did not exhibit increased cell-cell interactions compared with vectortransfected C6 cells (data not shown).…”

“…We first noted that T-cadherin expression was increased in malignant astrocytoma cells from B8 mice compared with postnatal day 2 normal cultured astrocytes or nonneoplastic B8 astrocytes (28). Several T-cadherin molecular species were noted (50,(53)(54), ranging from 95 to 130 kDa. Since the active form of the molecule is 105 kDa, it was unclear from these studies whether this increase in T-cadherin expression was associated with astrocyte tumorigenesis.…”

CDH13 gene coding t-cadherin influences variations in plasma adiponectin levels in the Japanese population

“…Since T-cadherin has been shown to bind low density lipoprotein (LDL) cholesterol [Resink et al, 1999], we next analyzed the association between rs12051272 genotypes and the levels of LDL cholesterol using the data from whole Suita study participants. The rs12051272 genotypes showed no significant association with serum LDL cholesterol levels (P = 0.19), as well as with total or HDL cholesterol levels (P = 0.46 and 0.16, respectively).…”

The Glycosyl Phosphatidylinositol Anchor of Human T-Cadherin Binds Lipoproteins

“…Amino acid sequencing of tryptic fragments of protein purified from human aortic medial tissue and immunoblot analysis of purified proteins indicated that p105 is identical with mature human T-cad (12) and that p130 is identical with the unprocessed T-cad precursor (11). In HEK293 cells stably transfected with human T-cad cDNA a colocalization of LDL-binding and anti-T-cad immunoreactivity to the expected mature (105 kDa) and precursor (130 kDa) forms of T-cad was shown (18). Additionally, intact T-cad transfected cells exhibited a significantly increased specific cell surface binding of [ 125 I]-LDL that was sensitive to phosphatidylinositolspecific phospholipase C pre-treatment of cells (18).…”