The cytoplasmic domain of human FcγRIa alters the functional properties of the FcγRI•γ-chain receptor complex

The gamma/zeta-chain family of proteins mediate cell activation for multiple immunoglobulin receptors, However, the recognition that these receptors may have distinct biologic functions suggests that additional signaling elements may contribute to functional diversity. We hypothesized that the cytoplasmic domain (CY) of the ligand binding alpha-chain alters the biological properties of the receptor complex. Using macrophage Fc gamma RIa as a model system, we created stable transfectants expressing a full-length or a CY deletion mutant of human Fc gamma RIa. Both receptors functionally associate with the endogenous murine gamma-chain. However, we have established that the CY of Fc gamma RIa directly contributes to the functional properties of the receptor complex. Deletion of the Fc gamma RIa CY leads to slower kinetics of receptor-specific phagocytosis and endocytosis as well as lower total phagocytosis despite identical levels of receptor expression. Deletion of the CY also converts the phenotype of calcium independent Fc gamma RIa-specific phagocytosis to a calcium-dependent phenotype, Finally, deletion of the CY abrogates Fc gamma RIa-specific secretion of interleukin-6 but does not, affect production of interleukin-1 beta These results demonstrate a functional role for the CY of Fc gamma RIa and provide a general model for understanding how multiple receptors that utilize the gamma-chain can generate diversity in function.