The Fc?RI Signaling Cascade and Integrin Trafficking Converge at Patterned Ligand Surfaces.

ABSTRACT: We examined the spatial targeting of early and downstream signaling mediated by the IgE receptor (Fc?RI) in RBL mast cells utilizing surface-patterned 2,4 dinitrophenyl (DNP) ligands. Micron-sized features of DNP are presented as densely immobilized conjugates of bovine serum albumin (DNP-BSA) or mobile in a supported lipid bilayer (DNP-SLB). Although soluble anti-DNP IgE binds uniformly across features for both pattern types, IgE bound to Fc?RI on cells shows distinctive distributions: uniform for DNP-SLB and edge-concentrated for DNP-BSA. These distributions of IgE-Fc?RI propagate to the spatial recruitment of early signaling proteins, including spleen tyrosine kinase (Syk), linker for activation of T cells (LAT), and activated phospholipase C gamma 1 (PLC?1), which all localize with engaged receptors. We found stimulated polymerization of F-actin is not required for Syk recruitment but is progressively involved in the recruitment of LAT and PLC?1. We further found ?1- and ?3-integrins colocalize with IgE-Fc?RI at patterned ligand surfaces as cells spread. This recruitment corresponds to directed exocytosis of recycling endosomes (REs) containing these integrins and their fibronectin ligand. Together, our results show targeting of signaling components, including integrins, to regions of clustered IgE-Fc?RI in processes that depend on stimulated actin polymerization and outward trafficking of REs.

SUBMITTER: Wakefield DL 

PROVIDER: S-EPMC5687038 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature