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New Regulatory Roles of Galectin-3 in High-Affinity IgE Receptor Signaling
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SYSNO ASEP 0471873 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title New Regulatory Roles of Galectin-3 in High-Affinity IgE Receptor Signaling Author(s) Bambousková, Monika (UMG-J)
Polakovičová, Iva (UMG-J)
Hálová, Ivana (UMG-J) RID, ORCID
Goel, G. (US)
Dráberová, Lubica (UMG-J) RID
Bugajev, Viktor (UMG-J) RID
Doan, A. (US)
Utekal, Pavol (UMG-J)
Gardet, A. (US)
Xavier, R.J. (US)
Dráber, Petr (UMG-J) RIDNumber of authors 11 Source Title Molecular and Cellular Biology. - : American Society for Microbiology - ISSN 0270-7306
Roč. 36, č. 9 (2016), s. 1366-1382Number of pages 17 s. Language eng - English Country US - United States Keywords fc-epsilon-ri ; t-cell-activation ; basophilic leukemia-cells ; mast-cell ; immunoglobulin-e ; tyrosine kinase ; lipid rafts ; monoclonal-antibody ; negative regulation ; mediator release Subject RIV EB - Genetics ; Molecular Biology R&D Projects GBP302/12/G101 GA ČR - Czech Science Foundation (CSF) Institutional support UMG-J - RVO:68378050 UT WOS 000374110900005 DOI 10.1128/MCB.00064-16 Annotation Aggregation of the high-affinity receptor for IgE (Fc epsilon RI) in mast cells initiates activation events that lead to degranulation and release of inflammatory mediators. To better understand the signaling pathways and genes involved in mast cell activation, we developed a high-throughput mast cell degranulation assay suitable for RNA interference experiments using lentivirus-based short hairpin RNA (shRNA) delivery. We tested 432 shRNAs specific for 144 selected genes for effects on Fc epsilon RI-mediated mast cell degranulation and identified 15 potential regulators. In further studies, we focused on galectin-3 (Gal3), identified in this study as a negative regulator of mast cell degranulation. Fc epsilon RI-activated cells with Gal3 knockdown exhibited upregulated tyrosine phosphorylation of spleen tyrosine kinase and several other signal transduction molecules and enhanced calcium response. We show that Gal3 promotes internalization of IgE-Fc epsilon RI complexes; this may be related to our finding that Gal3 is a positive regulator of Fc epsilon RI ubiquitination. Furthermore, we found that Gal3 facilitates mast cell adhesion and motility on fibronectin but negatively regulates antigen-induced chemotaxis. The combined data indicate that Gal3 is involved in both positive and negative regulation of Fc epsilon RI-mediated signaling events in mast cells. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2017
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