Direct interaction of the extracellular matrix protein DANCE with apolipoprotein(a) mediated by the kringle IV-type 2 domain.
Lipoprotein(a) [Lp(a)] consists of LDL and apolipoprotein(a), and has been shown to be a major, independent, risk factor for arteriosclerosis and thrombosis in humans. To further elucidate the (patho)physiological function(s) of Lp(a)/apo(a), we searched for new protein ligands, using the yeast two-hybrid system and employing the highly repetitive kringle IV type 2 (KIV-2) sequence from apo(a) as bait. The extracellular matrix protein DANCE [developmental arteries and neural crest epidermal growth factor (EGF)-like] recently implicated in atherogenesis was identified as an interactor. A direct physical interaction between DANCE and apo(a) was confirmed by co-purification of both recombinant proteins derived from culture supernatants of transiently transfected COS-1 cells. Furthermore, binding of human plasma-derived Lp(a) to recombinant DANCE was also observed. Finally, when monoclonal anti-apo(a) and polyclonal anti-DANCE antibodies were applied to tissue slices of atherosclerotic carotid artery, the two proteins were found to be co-localized in endothelial and smooth muscle cells, suggesting that they occur together in the arterial wall. However, as yet, the in vivo relevance and the possible functional role of this newly identified DANCE:Lp(a)/apo(a) interaction remains speculative.
Institute for Medical Biology and Human Genetics, University of Innsbruck, Schoepfstr. 41, A-6020 Innsbruck Austria.
A
A
Kapetanopoulos
F
F
Fresser
G
G
Millonig
Y
Y
Shaul
G
G
Baier
G
G
Utermann
D000818:Animals; D001054:Apolipoproteins A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D002339:Carotid Arteries / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D018082:Kringles; D017270:Lipoprotein(a) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques
D001054:Apolipoproteins A; D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D017270:Lipoprotein(a); D011994:Recombinant Proteins