Miteva, KT, Pedicini, L, Wilson, LA et al. (9 more authors) (2019) Rab46 integrates Ca2+ and histamine signaling to regulate selective cargo release from Weibel-Palade bodies. Journal of Cell Biology, 218 (7). pp. 2232-2246. ISSN 0021-9525
Abstract
Endothelial cells selectively release cargo stored in Weibel-Palade bodies (WPBs) to regulate vascular function, but the underlying mechanisms are poorly understood. Here we show that histamine evokes the release of the proinflammatory ligand, P-selectin, while diverting WPBs carrying non-inflammatory cargo away from the plasma membrane to the microtubule organizing center. This differential trafficking is dependent on Rab46 (CRACR2A), a newly identified Ca2+-sensing GTPase, which localizes to a subset of P-selectin–negative WPBs. After acute stimulation of the H1 receptor, GTP-bound Rab46 evokes dynein-dependent retrograde transport of a subset of WPBs along microtubules. Upon continued histamine stimulation, Rab46 senses localized elevations of intracellular calcium and evokes dispersal of microtubule organizing center–clustered WPBs. These data demonstrate for the first time that a Rab GTPase, Rab46, integrates G protein and Ca2+ signals to couple on-demand histamine signals to selective WPB trafficking
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 Miteva et al. https://creativecommons.org/licenses/by/4.0/ This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Funding Information: | Funder Grant number MRC (Medical Research Council) MR/N000285/ British Heart Foundation FS/17/43/33003 |
Depositing User: | Symplectic Publications |
Date Deposited: | 23 May 2019 10:17 |
Last Modified: | 02 Feb 2021 22:14 |
Status: | Published |
Publisher: | Rockefeller University Press |
Identification Number: | 10.1083/jcb.201810118 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:146478 |