@article {Tiruppathi619510, author = {Chinnaswamy Tiruppathi and Sushil C. Regmi and Dong-Mei Wang and Gary C.H. Mo and Peter T. Toth and Stephen M. Vogel and Radu V. Stan and Mark Henkemeyer and Richard D. Minshall and Asrar B. Malik}, title = {EphB1 in Endothelial Cells Regulates Caveolae Formation and Endocytosis}, elocation-id = {619510}, year = {2019}, doi = {10.1101/619510}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Caveolae, the cave-like structures abundant in endothelial cells (ECs), are important in regulating key functions such as caveolae-mediated endocytosis and generation of nitric oxide. Here we show that deletion of the receptor tyrosine kinase EphB1 (EphB1-/-) in mice markedly reduced the caveolae number in ECs of heart and lung vessels and prevented caveolae-mediated endocytosis. EphB1 expressed in adult ECs was shown to bind the caveolin-1 (Cav-1) scaffold domain (CSD) via the CSD binding motif (CSDBM) on EphB1. We demonstrated that activation of EphB1 by the native ligand Ephrin B1 uncoupled EphB1 from Cav-1, and licensed Src-dependent Y-14 Cav-1 phosphorylation. Deletion of CSDBM on EphB1 prevented EphB1/Cav-1 interaction and the activation of Src and Src mediated Y-14 Cav-1 phosphorylation. These studies identify the central role of endothelium expressed EphB1 in regulating caveolae biogenesis and caveolae-mediated endocytosis.}, URL = {https://www.biorxiv.org/content/early/2019/04/26/619510}, eprint = {https://www.biorxiv.org/content/early/2019/04/26/619510.full.pdf}, journal = {bioRxiv} }