Regulation of the expression of murine alpha- and beta-Fc gamma R genes.
Murine low-affinity receptors for the Fc portion of IgG are of two types: Fc gamma RII and Fc gamma RIII. Murine Fc gamma RII and III have 95% homologous extracellular (EC) domains and bind the same ligands, but different transmembrane (TM) and intracytoplasmic (IC) domains. They, however, have unrelated TM and IC domains. Murine Fc gamma RII are single-chain receptors, encoded by the beta-Fc gamma R gene. Murine Fc gamma RIII are composed of two subunits: the ligand-binding alpha-subunit, encoded by the alpha-Fc gamma R gene and the gamma-subunit, encoded by another gene which belongs to a family of genes encoding dimeric subunits of multichain receptors. The expression of murine Fc gamma RII and Fc gamma RIII depends on a number of mechanisms which do the following: (1) determine the tissue-specific expression of the alpha- and beta-Fc gamma R genes by selectively unmethylating DNA in specific 5' sequences in different cell types; (2) regulate the initiation of the transcription of the alpha- and beta-Fc gamma R genes via several transcription factors; (3) up- and downregulate the amount of alpha- and beta-Fc gamma R transcripts in response to cytokines; (4) decide the alternative splicing of IC exons of the beta-Fc gamma R gene and generate the different Fc gamma RII isoforms; (5) possibly regulate the translation of alpha- and beta-Fc gamma R transcripts in different cells; (6) control the assembly of the Fc gamma RIII subunits and their membrane insertion, and (7) determine the turnover of Fc gamma RII and III in the presence and absence of ligands by affecting the internalization, shedding and proteolytic cleavage of the receptors. These mechanisms altogether contribute to make a variety of cells capable of responding differently to antigen-antibody complexes, depending on environmental stimuli.
Daëron
M
M
Laboratoire d'Immunologie Cellulaire et Clinique, INSERM U.255, Institut Curie, Paris, France.
D000818:Animals; D002462:Cell Membrane / Q000276:immunology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005786:Gene Expression Regulation; D008745:Methylation; D051379:Mice; D014176:Protein Biosynthesis; D012326:RNA Splicing; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D017452:Receptors, IgG; D004247:DNA