Endoglin expression on human microvascular endothelial cells - Associationwith betaglycan and formation of higher order complexes with TGF-beta signalling receptors

Transforming growth factor-beta (TGF-beta) plays an important role in angio genesis and vascular function. Endoglin, a transmembrane TGF-beta binding p rotein, is highly expressed on vascular endothelial cells and is the target gene for the hereditary haemorrhagic telangiectasia type I (HHT1), a domin antly inherited vascular disorder. The specific function of endoglin respon sible for HHT1 is believed to involve alterations in TGF-beta responses. Th e initial interactions on the cell surface between endoglin and TGF-beta re ceptors may be an important mechanism by which endoglin modulates TGF-beta signalling, and thereby responses. Here it is shown that on human microvasc ular endothelial cells, endoglin is co-expressed and is associated with bet aglycan, a TGF-beta accessory receptor with which endoglin shares limited a mino acid homology. This complex formation may occur in either a ligand-dep endent or a ligand-independent manner. In addition, the occurrence of three higher order complexes containing endoglin, type II and/or type I TGF-beta receptors, on these cells is demonstrated. Our findings suggest that endog lin may modify TGF-beta signalling by interacting with both betaglycan and the TGF-beta signalling receptors at physiological receptor concentrations and ratios.