The cytoplasmic domain of human FcgammaRIa alters the functional properties of the FcgammaRI.gamma-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 FcgammaRIa as a model system, we created stable transfectants expressing a full-length or a CY deletion mutant of human FcgammaRIa. Both receptors functionally associate with the endogenous murine gamma-chain. However, we have established that the CY of FcgammaRIa directly contributes to the functional properties of the receptor complex. Deletion of the FcgammaRIa 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 FcgammaRIa-specific phagocytosis to a calcium-dependent phenotype. Finally, deletion of the CY abrogates FcgammaRIa-specific secretion of interleukin-6 but does not affect production of interleukin-1beta. These results demonstrate a functional role for the CY of FcgammaRIa and provide a general model for understanding how multiple receptors that utilize the gamma-chain can generate diversity in function.
Edberg
J C
JC
Departments of Medicine and Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama 35209, USA. JEdberg@uab.edu
Yee
A M
AM
Rakshit
D S
DS
Chang
D J
DJ
Gokhale
J A
JA
Indik
Z K
ZK
Schreiber
A D
AD
Kimberly
R P
RP
D000818:Animals; D002460:Cell Line; D004705:Endocytosis; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D010587:Phagocytosis; D017452:Receptors, IgG / Q000737:chemistry / Q000378:metabolism*
D015850:Interleukin-6; D017452:Receptors, IgG