A Heparin Receptor in Vascular Cells

我们在血管细胞中鉴定出TMEM184A作为肝素受体

SUMMARY Our identification of TMEM184A as a heparin receptor in vascular cells has led to investigations of how the heparin receptor works in vivo and to further studies of signaling. Saturating the heparin receptor decreases vascular cell proliferation in culture and knocking it down increases endothelial cell proliferation in regenerative angiogenesis. Despite increased cell proliferation, knockdown of the receptor decreases both developmental and regenerative angiogenesis. Our recent studies provide evidence suggesting involvement of the heparin receptor in VEGF signaling as well as in mechano-signaling. Both seem likely to involve direct interactions of the heparin receptor with heparan sulfate proteoglycans. The current proposal is designed to expand our knowledge about the heparin receptor and its function using a combination of cell culture assays, assays of developmental and regenerative angiogenesis in zebrafish, and employing a null mutant for the heparin receptor currently being developed. Specifically, we will test the hypothesis that the heparin receptor interacts with heparan sulfate proteoglycans to modulate signaling. We will also test the hypothesis that mechano-transduction through integrins and VE-Cadherin involves TMEM184A with syndecan 4, and recycling of the components. We will investigate TMEM184A signaling through VEGFR2 where we propose that it modulates the signaling through altering endocytosis pathways leading to altered signaling. Together these studies will provide data to better understand the mechanism(s) by which the heparin receptor is functioning and should yield clues to designing treatments for various vascular diseases that take advance of this heparin receptor modulatory system.