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

Autor:	Sulimenko V; Laboratory of Biology of Cytoskeleton, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia., Sládková V; Laboratory of Biology of Cytoskeleton, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia., Sulimenko T; Laboratory of Biology of Cytoskeleton, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia., Dráberová E; Laboratory of Biology of Cytoskeleton, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia., Vosecká V; Laboratory of Biology of Cytoskeleton, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia., Dráberová L; Laboratory of Signal Transduction, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia., Skalli O; Department of Biological Sciences, The University of Memphis, Memphis, TN, United States., Dráber P; Laboratory of Biology of Cytoskeleton, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Feb 02; Vol. 15, pp. 1321321. Date of Electronic Publication: 2024 Feb 02 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1321321
Abstrakt:	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 γ-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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Sulimenko, Sládková, Sulimenko, Dráberová, Vosecká, Dráberová, Skalli and Dráber.)
Databáze:	MEDLINE
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