EphB1 in Endothelial Cells Regulates Caveolae Formation and Endocytosis

Tiruppathi, C.; Regmi, S. C.; Wang, D.-M.; Mo, G. C. H.; Toth, P. T.; Vogel, S. M.; Stan, R. V.; Henkemeyer, M.; Minshall, R. D.; Malik, A. B.

doi:10.1101/619510

bioRxiv · 10.1101/619510

EphB1 in Endothelial Cells Regulates Caveolae Formation and Endocytosis

Tiruppathi, C.·Regmi, S. C.·Wang, D.-M.·Mo, G. C. H.·Toth, P. T.·Vogel, S. M.·Stan, R. V.·Henkemeyer, M.·Minshall, R. D.·Malik, A. B.

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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.

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Tiruppathi, C., Regmi, S. C., Wang, D.-M., Mo, G. C. H., Toth, P. T., Vogel, S. M., Stan, R. V., Henkemeyer, M., Minshall, R. D., Malik, A. B.. 2019-04-26. EphB1 in Endothelial Cells Regulates Caveolae Formation and Endocytosis. https://doi.org/10.1101/619510

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