The transmembrane adaptor protein NTAL limits mast cell chemotaxis toward prostaglandin E₂

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 E₂ (PGE₂). Although PGE₂ 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 PGE₂ Stimulation of mast cells that lacked NTAL with PGE₂ 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 β1-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 PGE₂ Together, these data suggest that NTAL is a key inhibitor of mast cell chemotaxis toward PGE₂, which may act through the RHOA/ERM/β1-integrin and PI3K/AKT axes.