Functional Association between the Human Myeloid Immunoglobulin A Fc Receptor (CD89) and FcR γChain

FcR γ chain has previously been shown to interact with the TCR-CD3 complex, the IgE Fc receptor I (Fc∊RI), and the class I and IIIA IgG receptors (FcγRI and FcγRIIIa). Here, we demonstrate that the Fc receptor γchain associates with FcαR in transfected IIA1.6 B lymphocytes. FcαR could be expressed at the surface of IIA1.6 B cells by itself, but was devoid of signaling capacity. Upon co-expression of FcR γchain, a physical interaction with FcαR could be demonstrated. This association proved crucial for the triggering of both proximal (intracellular calcium increase and tyrosine phosphorylation), as well as distal (IL-2 release), signal transduction responses. We next tested the hypothesis that a positively charged arginine residue (Arg209) within the transmembrane domain of FcαR promotes association with FcR γchain. We therefore constructed FcαR molecules where Arg209 was mutated to either a positively charged histidine, a negatively charged aspartic acid, or an uncharged leucine. A functional association between FcαR and FcR γchain was observed only with a positively charged residue (Arg209 or His209) present within the FcαR transmembrane domain. These data show that transmembrane signal transduction by the FcαR is mediated via FcR γchain, and that FcαR requires a positively charged residue within the transmembrane domain to promote functional association. FcR γ chain has previously been shown to interact with the TCR-CD3 complex, the IgE Fc receptor I (Fc∊RI), and the class I and IIIA IgG receptors (FcγRI and FcγRIIIa). Here, we demonstrate that the Fc receptor γchain associates with FcαR in transfected IIA1.6 B lymphocytes. FcαR could be expressed at the surface of IIA1.6 B cells by itself, but was devoid of signaling capacity. Upon co-expression of FcR γchain, a physical interaction with FcαR could be demonstrated. This association proved crucial for the triggering of both proximal (intracellular calcium increase and tyrosine phosphorylation), as well as distal (IL-2 release), signal transduction responses. We next tested the hypothesis that a positively charged arginine residue (Arg209) within the transmembrane domain of FcαR promotes association with FcR γchain. We therefore constructed FcαR molecules where Arg209 was mutated to either a positively charged histidine, a negatively charged aspartic acid, or an uncharged leucine. A functional association between FcαR and FcR γchain was observed only with a positively charged residue (Arg209 or His209) present within the FcαR transmembrane domain. These data show that transmembrane signal transduction by the FcαR is mediated via FcR γchain, and that FcαR requires a positively charged residue within the transmembrane domain to promote functional association.