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Regulation of microtubule nucleation in mouse bone marrow-derived mast cells by ARF GTPase-activating protein GIT2
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SYSNO ASEP 0582327 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Ostatní články Title Regulation of microtubule nucleation in mouse bone marrow-derived mast cells by ARF GTPase-activating protein GIT2 Author(s) Sulimenko, Vadym (UMG-J) RID, ORCID
Sládková, Vladimíra (UMG-J)
Sulimenko, Tetyana (UMG-J)
Dráberová, Eduarda (UMG-J) RID, ORCID
Vosecká, Věra (UMG-J)
Dráberová, Lubica (UMG-J) RID
Skalli, O. (US)
Dráber, Pavel (UMG-J) RID, ORCIDArticle number 1321321 Source Title Frontiers in Immunology. - : Frontiers Media - ISSN 1664-3224
Roč. 15, Feb (2024)Number of pages 20 s. Language eng - English Country CH - Switzerland Keywords mast cells ; G protein-coupled receptor kinase-interacting protein 2 (GIT2) ; microtubule nucleation ; protein kinase C (PKC) ; centrosome OECD category Immunology R&D Projects GA21-30281S GA ČR - Czech Science Foundation (CSF) GA23-07736S GA ČR - Czech Science Foundation (CSF) LTAUSA19118 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LUC23123 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LX22NPO5102 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2023050 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UMG-J - RVO:68378050 DOI https://doi.org/10.3389/fimmu.2024.1321321 Annotation Aggregation of high-affinity IgE receptors (FcϵRIs) on granulated mast cells triggers signaling pathways leading to a calcium response and release of inflammatory mediators from secretory granules. While microtubules play a role in the degranulation process, the complex molecular mechanisms regulating microtubule remodeling in activated mast cells are only partially understood. Here, we demonstrate that the activation of bone marrow mast cells induced by FcϵRI aggregation increases centrosomal microtubule nucleation, with G protein-coupled receptor kinase-interacting protein 2 (GIT2) playing a vital role in this process. Both endogenous and exogenous GIT2 were associated with centrosomes and g-tubulin complex proteins. Depletion of GIT2 enhanced centrosomal microtubule nucleation, and phenotypic rescue experiments revealed that GIT2, unlike GIT1, acts as a negative regulator of microtubule nucleation in mast cells. GIT2 also participated in the regulation of antigen-induced degranulation and chemotaxis. Further experiments showed that phosphorylation affected the centrosomal localization of GIT2 and that during antigen-induced activation, GIT2 was phosphorylated by conventional protein kinase C, which promoted microtubule nucleation. We propose that GIT2 is a novel regulator of microtubule organization in activated mast cells by modulating centrosomal microtubule nucleation. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2025 Electronic address https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1321321/full
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