LDL induces intracellular signalling and cell migration via atypical LDL-binding protein T-cadherin

Cadherins are a superfamily of adhesion molecules that mediate Ca(2+)-dependent cell-cell adhesion. T-cadherin (T-cad), a unique glycosylphosphatidylinositol-anchored member of the cadherin superfamily, was initially identified by immunoblotting of vascular cell membranes as an atypical low affinity...

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Published in:Molecular and cellular biochemistry 2005-05, Vol.273 (1-2), p.33-41
Main Authors: Rubina, K, Talovskaya, E, Cherenkov, V, Ivanov, D, Stambolsky, D, Storozhevykh, T, Pinelis, V, Shevelev, A, Parfyonova, Ye, Resink, T, Erne, P, Tkachuk, V
Format: Article
Language:English
Subjects:
Adhesion
Animals
Atherosclerosis
Cadherins - metabolism
Calcium - pharmacology
Cell adhesion & migration
Cell Movement
Cells
Cells, Cultured
Humans
Immunoblotting
Iodine Radioisotopes
Lipoproteins, LDL - metabolism
Mice
Protein Binding
Proteins
Risk factors
Signal Transduction
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Summary:Cadherins are a superfamily of adhesion molecules that mediate Ca(2+)-dependent cell-cell adhesion. T-cadherin (T-cad), a unique glycosylphosphatidylinositol-anchored member of the cadherin superfamily, was initially identified by immunoblotting of vascular cell membranes as an atypical low affinity low density lipoprotein (LDL)-binding protein. It is not known whether this heterophilic interaction is physiologically relevant. Expression of T-cadherin is upregulated in vascular cells during atherosclerosis, restenosis and tumour angiogenesis, conditions characterized by enhanced cell migration and growth. Elevated levels of serum low density lipoproteins (LDL), which result in cholesterol accumulation in vascular wall, is a widely accepted risk factor in atherosclerosis development. Additionally to its metabolic effects, LDL can produce hormone-like effects in a number of cell types. This study has utilized HEK293 cells and L929 cells stably transfected with T-cadherin cDNA to investigate T-cad-dependent responses to LDL. Stable expression of T-cad in both HEK293 and L929 cells results in significantly (p < 0.05) elevated specific surface binding of [I125]-LDL. Compared with mock-transfectants, cells expressing T-cad exhibit significantly (p < 0.01) enhanced LDL-induced mobilization of intracellular Ca(2+)-stores and a significantly (p < 0.01) increased migration toward an LDL gradient (0.1% BSA + 60 microg/ml LDL) in Boyden chamber migration assay. Thus LDL-binding to T-cad is capable of activating physiologically relevant intracellular signaling and functional responses.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-005-0250-5