p18, a novel adaptor protein, regulates pulmonary endothelial barrier function via enhanced endocytic recycling of VE-cadherin.

Chichger, Havovi and Duong, Huetran and Braza, Julie and Harrington, Elizabeth O (2015) p18, a novel adaptor protein, regulates pulmonary endothelial barrier function via enhanced endocytic recycling of VE-cadherin. The FASEB Journal. ISSN 1530-6860 (Draft)

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Abstract

Vascular permeability is a hallmark of several disease states including acute lung injury (ALI). Endocytosis of VE-cadherin, away from the interendothelial junction (IEJ), causes acute endothelial barrier permeability. A novel protein, p18, anchors to the endosome membrane and plays a role in late endosomal signaling via MAPK and mammalian target of rapamycin. However, the fate of the VE-cadherin-positive endosome has yet to be elucidated. We sought to elucidate a role for p18 in VE-cadherin trafficking and thus endothelial barrier function, in settings of ALI. Endothelial cell (EC) resistance, whole-cell ELISA, and filtration coefficient were studied in mice or lung ECs overexpressing wild-type or nonendosomal-binding mutant p18, using green fluorescent protein as a control. We demonstrate a protective role for the endocytic protein p18 in endothelial barrier function in settings of ALI in vitro and in vivo, through enhanced recycling of VE-cadherin-positive early endosomes to the IEJ. In settings of LPS-induced ALI, we show that Src tethered to the endosome tyrosine phosphorylates p18 concomitantly with VE-cadherin internalization and pulmonary edema formation. We conclude that p18 regulates pulmonary endothelial barrier function in vitro and in vivo, by enhancing recycling of VE-cadherin-positive endosomes to the IEJ.

Item Type: Journal Article
Additional Information: Citation: Chichger, H., Duong, H., Braza, J., & Harrington, E. O. (2015). p18, a novel adaptor protein, regulates pulmonary endothelial barrier function via enhanced endocytic recycling of VE-cadherin. The FASEB Journal, 29(3), 868-881.
Faculty: Faculty of Science & Technology
Depositing User: Mr I Walker
Date Deposited: 01 Jun 2016 08:50
Last Modified: 07 Jul 2016 12:54
URI: http://arro.anglia.ac.uk/id/eprint/611346

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