Divergent intracellular sorting of Fc{gamma}RIIA and Fc{gamma}RIIB2.
The human low affinity FcγRII family includes both the activating receptor FcγRIIA and the inhibitory receptor FcγRIIB2. These receptors have opposing signaling functions but are both capable of internalizing IgG-containing immune complexes through clathrin-mediated endocytosis. We demonstrate that upon engagement by multivalent aggregated human IgG, FcγRIIA expressed in ts20 Chinese hamster fibroblasts is delivered along with its ligand to lysosomal compartments for degradation, while FcγRIIB2 dissociates from the ligand and is routed separately into the recycling pathway. FcγRIIA sorting to lysosomes requires receptor multimerization, but does not require either Src family kinase activity or ubiquitylation of receptor lysine residues. The sorting of FcγRIIB2 away from a degradative fate is not due to its lower affinity for IgG and occurs even upon persistent receptor aggregation. Upon co-engagement of FcγRIIA and FcγRIIB2, the receptors are sorted independently to distinct final fates after dissociation of co-clustering ligand. These results reveal fundamental differences in the trafficking behavior of different Fcγ receptors.
Zhang
Christine Y
CY
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Booth
James W
JW
D000818:Animals; D006224:Cricetinae; D004705:Endocytosis; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D008024:Ligands; D008247:Lysosomes / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011817:Rabbits; D017452:Receptors, IgG / Q000737:chemistry*
C080568:Fc gamma receptor IIA; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D008024:Ligands; D017452:Receptors, IgG