Direct interaction between FcgammaRI (CD64) and periplakin controls receptor endocytosis and ligand binding capacity

Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10392-7. doi: 10.1073/pnas.0401217101. Epub 2004 Jun 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / physiology
  • Cell Membrane / metabolism
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / metabolism*
  • Cytosol / metabolism
  • Endocytosis / physiology*
  • Gene Expression
  • Humans
  • Leukocytes / physiology
  • Ligands
  • Myeloid Cells / physiology
  • Plakins
  • Precipitin Tests
  • Protein Structure, Tertiary
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism*
  • Signal Transduction / physiology*


  • Cytoskeletal Proteins
  • Ligands
  • PPL protein, human
  • Plakins
  • Receptors, IgG