The transmembrane adaptor protein NTAL limits mast cell chemotaxis toward prostaglandin E-2

0497556 - ÚMG 2019 RIV US eng J - Journal Article
Hálová, Ivana - Bambousková, Monika - Dráberová, Lubica - Bugajev, Viktor - Dráber, Petr
The transmembrane adaptor protein NTAL limits mast cell chemotaxis toward prostaglandin E-2.
Science Signaling. Roč. 11, č. 556 (2018), č. článku eaao4354. ISSN 1945-0877. E-ISSN 1937-9145
R&D Projects: GA ČR(CZ) GA17-20255S; GA ČR(CZ) GA17-20915S; GA ČR(CZ) GA18-18521S
Institutional support: RVO:68378050
Keywords : affinity ige receptor * activation linker * phosphoinositide 3-kinase * tyrosine phosphorylation * actin rearrangement * monoclonal-antibody * negative regulation * allergic response * regulatory roles * mediator release
OECD category: Endocrinology and metabolism (including diabetes, hormones)
Impact factor: 6.565, year: 2018

Chemotaxis of mast cells is one of the crucial steps in their development and function. Non-T cell activation linker (NTAL) is a transmembrane adaptor protein that inhibits the activation of mast cells and B cells in a phosphorylation-dependent manner. Here, we studied the role of NTAL in the migration of mouse mast cells stimulated by prostaglandin E-2 (PGE(2)). Although PGE(2) does not induce the tyrosine phosphorylation of NTAL, unlike IgE immune complex antigens, we found that loss of NTAL increased the chemotaxis of mast cells toward PGE(2). Stimulation of mast cells that lacked NTAL with PGE(2) enhanced the phosphorylation of AKT and the production of phosphatidylinositol 3,4,5-trisphosphate. In resting NTAL-deficient mast cells, phosphorylation of an inhibitory threonine in ERM family proteins accompanied increased activation of beta 1-containing integrins, which are features often associated with increased invasiveness in tumors. Rescue experiments indicated that only full-length, wild-type NTAL restored the chemotaxis of NTAL-deficient cells toward PGE(2). Together, these data suggest that NTAL is a key inhibitor of mast cell chemotaxis toward PGE(2), which may act through the RHOA/ERM/beta 1-integrin and PI3K/AKT axes.
Permanent Link: http://hdl.handle.net/11104/0290108