Regulation of microtubule nucleation in mouse bone marrow-derived mast cells by ARF GTPase-activating protein GIT2

0585201 - ÚMG 2025 RIV CH eng J - Journal Article
Sulimenko, Vadym - Sládková, Vladimíra - Sulimenko, Tetyana - Dráberová, Eduarda - Vosecká, Věra - Dráberová, Lubica - Skalli, O. - Dráber, Pavel
Regulation of microtubule nucleation in mouse bone marrow-derived mast cells by ARF GTPase-activating protein GIT2.
Frontiers in Immunology. Roč. 15, Feb (2024), č. článku 1321321. ISSN 1664-3224. E-ISSN 1664-3224
R&D Projects: GA MŠMT LX22NPO5102; GA ČR GA21-30281S; GA ČR(CZ) GA23-07736S; GA MŠMT LTAUSA19118; GA MŠMT(CZ) LUC23123; GA MŠMT(CZ) LM2023050
Institutional support: RVO:68378050
Keywords : gamma-tubulin * kinase-c * immune-system * complexes * identification * degranulation * receptor * src * fyn * localization * mast cells * centrosome * G protein-coupled receptor kinase-interacting protein 2 (GIT2) * microtubule nucleation * protein kinase C (PKC)
OECD category: Immunology
Impact factor: 7.3, year: 2022
Method of publishing: Open access
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1321321/full

Aggregation of high-affinity IgE receptors (Fc epsilon RIs) 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 Fc epsilon RI 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 gamma-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.
Permanent Link: https://hdl.handle.net/11104/0352947