Effector proteins of FcγRI: inside-out and outside-in regulation (134.81)

Abstract

Abstract FcγRI is the only IgG receptor that is capable of binding monomeric IgG. It depends on the FcR γ-chain for its function. However, some functions such as antigen presentation, are mediated by the ligand binding α-chain. Here we describe two binding partners of FcγRI: periplakin (PPL) and protein 4.1G. Yeast-two hybrid screenings identified PPL and 4.1G as binding partners of the cytosolic tail of FcγRI. Alanine scans and truncations of the tail were made to study the binding site of the proteins to the receptor. Plate immobilized IgG adhesion assays were used to measure affinity of FcγRI stabily expressed on IIa1.6 cell lines with and without c-terminal PPL. PPL and 4.1G were found to bind to the proximal region of the receptor. PPL affected the binding of FcγRI to opsonised RBCs and adhesion to IgG coated plates. Experiments with tat-peptides blocking PPL- FcγRI interaction suggested that endogenous PPL lowers FcγRI affinity. Among the Fcγ receptors, FcγRI is unique in its capability to bind monomeric IgG and in its cytosolic tail sequence. We propose a role for PPL in modulating the affinity of FcγRI, leading to accessibility of the receptor for immunecomplexes. Funding NWO #07764/ALW