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Open AccessFeature PaperArticle

Regulation of Microtubule Nucleation in Mouse Bone Marrow-Derived Mast Cells by Protein Tyrosine Phosphatase SHP-1

1
Department of Biology of Cytoskeleton, Institute of Molecular Genetics, Czech Academy of Sciences, CZ-142 20 Prague, Czech Republic
2
Light Microscopy Core Facility, Institute of Molecular Genetics, Czech Academy of Sciences, CZ-142 20 Prague, Czech Republic
*
Authors to whom correspondence should be addressed.
Cells 2019, 8(4), 345; https://doi.org/10.3390/cells8040345
Received: 3 February 2019 / Revised: 30 March 2019 / Accepted: 10 April 2019 / Published: 11 April 2019
(This article belongs to the Special Issue Tubulin: Structure, Functions and Roles in Disease)
The antigen-mediated activation of mast cells initiates signaling events leading to their degranulation, to the release of inflammatory mediators, and to the synthesis of cytokines and chemokines. Although rapid and transient microtubule reorganization during activation has been described, the molecular mechanisms that control their rearrangement are largely unknown. Microtubule nucleation is mediated by γ-tubulin complexes. In this study, we report on the regulation of microtubule nucleation in bone marrow-derived mast cells (BMMCs) by Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 1 (SHP-1; Ptpn6). Reciprocal immunoprecipitation experiments and pull-down assays revealed that SHP-1 is present in complexes containing γ-tubulin complex proteins and protein tyrosine kinase Syk. Microtubule regrowth experiments in cells with deleted SHP-1 showed a stimulation of microtubule nucleation, and phenotypic rescue experiments confirmed that SHP-1 represents a negative regulator of microtubule nucleation in BMMCs. Moreover, the inhibition of the SHP-1 activity by inhibitors TPI-1 and NSC87877 also augmented microtubule nucleation. The regulation was due to changes in γ-tubulin accumulation. Further experiments with antigen-activated cells showed that the deletion of SHP-1 stimulated the generation of microtubule protrusions, the activity of Syk kinase, and degranulation. Our data suggest a novel mechanism for the suppression of microtubule formation in the later stages of mast cell activation. View Full-Text
Keywords: bone marrow-derived mast cells; cell activation; γ-tubulin complexes; microtubule nucleation; SHP-1 tyrosine phosphatase bone marrow-derived mast cells; cell activation; γ-tubulin complexes; microtubule nucleation; SHP-1 tyrosine phosphatase
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Klebanovych, A.; Sládková, V.; Sulimenko, T.; Vosecká, V.; Rubíková, Z.; Čapek, M.; Dráberová, E.; Dráber, P.; Sulimenko, V. Regulation of Microtubule Nucleation in Mouse Bone Marrow-Derived Mast Cells by Protein Tyrosine Phosphatase SHP-1. Cells 2019, 8, 345.

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