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Aggregation of tetraspanin CD9 causes activation of mast cells and inhibits their chemotaxis toward antigen and stem cell factor
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SYSNO ASEP 0392779 Druh ASEP C - Konferenční příspěvek (mezinárodní konf.) Zařazení RIV Záznam nebyl označen do RIV Název Aggregation of tetraspanin CD9 causes activation of mast cells and inhibits their chemotaxis toward antigen and stem cell factor Tvůrce(i) Hálová, Ivana (UMG-J) RID, ORCID Zdroj.dok. -. - Nijmegen, 2012 Akce 5th European Conference on Tetraspanins Datum konání 26.09.2012-28.09.2012 Místo konání Nijmegen Země NL - Nizozemsko Jazyk dok. eng - angličtina Země vyd. NL - Nizozemsko Klíč. slova tetraspanin ; mast cells ; CD9 Vědní obor RIV EB - Genetika a molekulární biologie CEP GA301/09/1826 GA ČR - Grantová agentura ČR GAP302/10/1759 GA ČR - Grantová agentura ČR GBP302/12/G101 GA ČR - Grantová agentura ČR Institucionální podpora UMG-J - RVO:68378050 Anotace CD9 is a prototypical tetraspanin, which has been found to regulate cell motility, adhesion, and fusion. Loss of CD9 expression is associated with tumor progression and metastasis in several types of cancer. Despite the fact that CD9 is one of the most abundant proteins on mast cell surface, its role in these cells is poorly understood. In this study we have shown that aggregation of CD9 by a newly developed monoclonal antibody leads to activation of mast cells as measured by degranulation, calcium release and phosphorylation of several proteins, including transmembrane adaptor NTAL (but not closely related LAT). NTAL (but not LAT) was found to colocalize with CD9 as measured by electron microscopy of immunogold-labeled membrane sheets. Antibody-mediated aggregation of CD9 resulted in inhibition of migration towards stem cell factor (SCF) and antigen. Unlike several other cell types and chemoattractants, migration of mast cells towards SCF and antigen was not affected by decreased CD9 surface expression. Aggregation of CD9 had no effect on degranulation, calcium influx and phosphorylation of MAPKs caused by antigen or SCF. CD9-mediated inhibition of migration was not dependent on the presence of NTAL as indicated by experiments with mast cells derived from NTAL-deficient mice. CD9 aggregation had no effect on early depolymerization of filamentous actin observed in antigen-activated cells. Interestingly, activation by SCF, antigen or CD9 led to transient dephosphorylation of the regulatory threonine of ezrin. Based on these and other data we conclude that aggregated CD9 causes mast cell activation and interferes with proper cross-talk between surface receptors and cytoskeleton in which ezrin dephosphorylation plays an important role. This results in decreased migration of the cells towards known chemoattractants, antigen and SCF. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2014
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