Pedicini, L., Smith, J., Savic, S. orcid.org/0000-0001-7910-0554 et al. (1 more author) (2023) Rab46: a novel player in mast cell function. Discovery Immunology, 3 (1). kyad028. ISSN 2754-2483
Abstract
Mast cells are infamous for mediating allergic and inflammatory diseases due to their capacity of rapidly releasing a wide range of inflammatory mediators stored in cytoplasmic granules. However, mast cells also have several important physiological roles that involve selective and agonist-specific release of these active mediators. While a filtering mechanism at the plasma membrane could regulate the selective release of some cargo, the plethora of stored cargo and the diversity of mast cell functions suggests the existence of granule subtypes with distinct trafficking pathways. The molecular mechanisms underlying differential trafficking and exocytosis of these granules are not known, neither is it clear how granule trafficking is coupled to the stimulus. In endothelial cells, a Rab GTPase, Rab46, responds to histamine but not thrombin signals, and this regulates the trafficking of a subpopulation of endothelial-specific granules. Here, we sought to explore, for the first time, if Rab46 plays a role in mast cell function. We demonstrate that Rab46 is highly expressed in human and murine mast cells, and Rab46 genetic deletion has an effect on mast cell degranulation that depends on both stimuli and mast cell subtype. This initial insight into the contribution of Rab46 to mast cell function and the understanding of the role of Rab46 in stimuli-dependent trafficking in other cell types necessitates further investigations of Rab46 in mast cell granular trafficking so that novel and specific therapeutic targets for treatment of the diverse pathologies mediated by mast cells can be developed.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | mast cells; EFCAB4B, Rab46; CRACR2A; histamine; degranulation; trafficking; Rab GTPases |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Inflammatory Arthritis (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) |
Depositing User: | Symplectic Publications |
Date Deposited: | 25 Jan 2024 16:09 |
Last Modified: | 22 Mar 2024 10:58 |
Status: | Published |
Publisher: | Oxford University Press |
Identification Number: | 10.1093/discim/kyad028 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:208297 |