Cross-talk between Tetraspanin CD9 and Transmembrane Adaptor Protein Non-T Cell Activation Linker (NTAL) in Mast Cell Activation and Chemotaxis

0392777 - ÚMG 2014 RIV US eng J - Journal Article
Hálová, Ivana - Dráberová, Lubica - Bambousková, Monika - Machyna, Martin - Stegurová, Lucie - Smrž, Daniel - Dráber, Petr
Cross-talk between Tetraspanin CD9 and Transmembrane Adaptor Protein Non-T Cell Activation Linker (NTAL) in Mast Cell Activation and Chemotaxis.
Journal of Biological Chemistry. Roč. 288, č. 14 (2013), s. 9801-9814. ISSN 0021-9258. E-ISSN 1083-351X
R&D Projects: GA ČR GA301/09/1826; GA ČR GAP302/10/1759; GA ČR(CZ) GBP302/12/G101; GA ČR(CZ) GD204/09/H084; GA MŠMT LD12073; GA TA ČR TA01010436; GA MPO FR-TI3/067
Grant - others:European Cooperation in Science and Technology(XE) Action BM1007
Institutional support: RVO:68378050
Keywords : mast cell * chemotaxis * Fc receptor
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 4.600, year: 2013

Chemotaxis, a process leading to movement of cells towards increasing concentrations of chemoattractants, is essential, among others, for recruitment of mast cells within target tissues where they play an important role in innate and adaptive immunity. In this study we prepared a new mAb specific for the tetraspanin CD9. Binding of the antibody to bone marrow derived mast cells (BMMCs) triggered activation events which included cell degranulation, Ca2+ response, dephosphorylation of ezrin/radixin/moesin (ERM) family proteins and potent tyrosine phosphorylation of the non-T cell activation linker (NTAL) but only weak phosphorylation of the linker for activation of T cells (LAT). As documented by electron microscopy of isolated plasma membrane sheets, CD9 colocalized with the high-affinity IgE receptor (FcεRI) and NTAL but not with LAT. Further tests showed that both anti-CD9 antibody and its F(ab)2 fragment inhibited mast cell chemotaxis towards antigen. Experiments with BMMCs deficient in NTAL and/or LAT revealed different roles of these two adaptors in antigen-driven chemotaxis. The combined data indicate that chemotaxis towards antigen is controlled in mast cells by a crosstalk among FcεRI, tetraspanin CD9, transmembrane adaptor proteins NTAL and LAT and cytoskeleton-regulatory proteins of the ERM family.
Permanent Link: http://hdl.handle.net/11104/0228415