Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability

Nat Cell Biol. 2001 Oct;3(10):891-6. doi: 10.1038/ncb1001-891.


Chaperone proteins are thought to promote the correct folding and assembly of newly synthesized proteins and to facilitate restoration of the folded state under environmental conditions that favour protein denaturation. They are among the most ubiquitous and highly conserved of all proteins. The eukaryotic endoplasmic reticulum (ER) chaperone gp96 in particular has long been thought to be indispensable for cell survival. Here we report that a screen for genes required for the immune response to bacterial endotoxins has identified a B-cell line deficient in gp96. Absence of gp96 is compatible with cellular survival even under stress conditions and causes a defect in the formation of only a small subset of cell surface receptors. Toll-like receptors are retained intracellularly in the absence of gp96, explaining the unresponsiveness of the mutant to microbial stimuli.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cell Separation
  • Cell Survival / physiology*
  • Drosophila Proteins*
  • Endoplasmic Reticulum / chemistry*
  • Endoplasmic Reticulum / metabolism
  • Flow Cytometry
  • Genes, Reporter / genetics
  • Green Fluorescent Proteins
  • Humans
  • Immunity, Innate*
  • Indicators and Reagents / metabolism
  • Lipopolysaccharides / metabolism
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Molecular Chaperones / immunology
  • Molecular Chaperones / metabolism*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Structure-Activity Relationship
  • Toll-Like Receptors
  • Transfection


  • Drosophila Proteins
  • Indicators and Reagents
  • Lipopolysaccharides
  • Luminescent Proteins
  • Membrane Glycoproteins
  • Molecular Chaperones
  • NF-kappa B
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins
  • Toll-Like Receptors
  • Green Fluorescent Proteins