Interferon-inducible transmembrane proteins of the innate immune response act as membrane organizers by influencing clathrin and v-ATPase localization and function

Innate Immun. 2012 Dec;18(6):834-45. doi: 10.1177/1753425912443392. Epub 2012 Mar 30.


The innate response interferon-inducible transmembrane (Ifitm) proteins have been characterized as influencing proliferation, signaling complexes and restricting virus infections. Treatment of cells lacking these proteins (IfitmDel) with IFN-β resulted in the loss of clathrin from membrane compartments and the inhibition of clathrin-mediated phagocytosis, suggesting a molecular interaction between clathrin and Ifitm proteins. The pH of endosomes of IfitmDel cells, with or without IFN activation, was neutralized, suggesting the function of the vacular ATPase proton pumps in such cells was compromised. Co-immunoprecipitation of Ifitm3 with Atp6v0b demonstrated a direct interaction between the Ifitm proteins and the v-ATPase. These data suggest that the Ifitm proteins help stabilize v-ATPase complexes in cellular membranes which, in turn, facilitates the appropriate subcellular localization of clathrin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Clathrin / metabolism
  • Endocytosis / genetics
  • Endosomes / metabolism*
  • Immunity, Innate / genetics
  • Macrophages / immunology*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Binding / genetics
  • Protein Transport / genetics
  • Vacuolar Proton-Translocating ATPases / metabolism*


  • Atp6v0b protein, mouse
  • Clathrin
  • Membrane Proteins
  • fragilis protein, mouse
  • Vacuolar Proton-Translocating ATPases