Galectin-8 interacts with podoplanin and modulates lymphatic endothelial cell functions.
Podoplanin is a small, mucin-like membrane glycoprotein highly expressed by lymphatic but not by blood vascular endothelial cells. Although it was shown to be indispensable for the correct formation and function of the lymphatic vasculature, its precise molecular function has remained unknown. In the present study, we identified the mammalian lectin galectin-8 as a novel, glycosylation-dependent interaction partner of podoplanin. Galectin-8 is a tandem-repeat type galectin, which interacts with cell surface glycoproteins, including certain integrins, as well as with extracellular matrix molecules such as fibronectin. Here we show that, similar to podoplanin, galectin-8 is more highly expressed by lymphatic than by blood vascular endothelial cells, and that it promotes lymphatic endothelial cell adhesion as well as haptotactic migration when immobilized onto a surface, while inhibiting the formation of tube-like structures by lymphatic endothelial cells in a collagen matrix when incorporated into the matrix. Importantly, functions of blood vascular endothelial cells, which lack podoplanin expression, are not affected by galectin-8. These data suggest a role for galectin-8 and podoplanin in supporting the connection of the lymphatic endothelium to the surrounding extracellular matrix, most likely in cooperation with other glycoproteins on the surface of lymphatic endothelial cells.
Cueni
Leah N
LN
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland.
Detmar
Michael
M
D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D002465:Cell Movement; D006224:Cricetinae; D003412:Cricetulus; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D037161:Galectins / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D055767:Immobilized Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D011485:Protein Binding; D000098853:Podoplanin
D037161:Galectins; D055767:Immobilized Proteins; D008562:Membrane Glycoproteins; C091991:LGALS8 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin