New Regulatory Roles of Galectin-3 in High-Affinity IgE Receptor Signaling

0471873 - ÚMG 2017 RIV US eng J - Journal Article
Bambousková, Monika - Polakovičová, Iva - Hálová, Ivana - Goel, G. - Dráberová, Lubica - Bugajev, Viktor - Doan, A. - Utekal, Pavol - Gardet, A. - Xavier, R.J. - Dráber, Petr
New Regulatory Roles of Galectin-3 in High-Affinity IgE Receptor Signaling.
Molecular and Cellular Biology. Roč. 36, č. 9 (2016), s. 1366-1382. ISSN 0270-7306. E-ISSN 1098-5549
R&D Projects: GA ČR(CZ) GBP302/12/G101
Institutional support: RVO:68378050
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
Impact factor: 4.398, year: 2016

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.
Permanent Link: http://hdl.handle.net/11104/0269227