Direct interaction between FcgammaRI (CD64) and periplakin controls receptor endocytosis and ligand binding capacity.
FcgammaRI depends for its biological function on both the intracellular domain of the alpha-chain and associated Fc receptor (FcR) gamma-chains. However, functional protein effectors of FcgammaRI's intracellular domain have not been identified. In this study, we identified periplakin (PPL) as a selective interacting protein for the intracellular tail of FcgammaRI but no other activatory FcRs. The interaction was confirmed by coimmunoprecipitation and blot-overlay assays. PPL and FcgammaRI colocalized at the plasma membrane in monocytes and cell transfectants, and both were up-regulated by IFN-gamma. By expressing C-terminal PPL in transfectants, we established a pivotal role for this protein in FcgammaRI ligand binding, endocytosis, and antigen presentation. These data illustrate that intracellular protein interactions with a multisubunit FcR alpha-chain can confer unique properties to the receptor.
Beekman
Jeffrey M
JM
Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht, 3584 EA, Utrecht, The Netherlands.
Bakema
Jantine E
JE
van de Winkel
Jan G J
JG
Leusen
Jeanette H W
JH
D017951:Antigen Presentation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D008024:Ligands; D022423:Myeloid Cells / Q000502:physiology; D051179:Plakins; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D003598:Cytoskeletal Proteins; D008024:Ligands; C491674:PPL protein, human; D051179:Plakins; D017452:Receptors, IgG