Hsp90-mediated cytosolic refolding of exogenous proteins internalized by dendritic cells

• Alessandra Giodini ^[1] ; Peter Cresswell ^[2]
  1. [1] Yale University

     Yale University

     Town of New Haven, Estados Unidos

     
  2. [2] Howard Hughes Medical Institute

     Howard Hughes Medical Institute

     Estados Unidos

     
• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 27, Nº. 1, 2007, págs. 201-211
• Idioma: inglés
• Enlaces
  • Texto completo
• Resumen

  • Dendritic cells efficiently internalize exogenous protein antigens by fluid-phase uptake and receptor-mediated endocytosis. Such antigens contribute to cross-presentation by being translocated into the cytosol for proteasomal degradation, which liberates immunogenic peptides that can bind to major histocompatibility complex (MHC) class I molecules after being transported into the endoplasmic reticulum (ER). MHC class I–peptide complexes are then expressed on the cell surface and presented to CD8+ T cells. Here we show that internalized proteins can have an alternative fate. After internalization, proteins are first unfolded to allow translocation into the cytosol using a pathway related to ER-associated degradation (ERAD). Subsequently the unfolded proteins can undergo cytosolic refolding assisted by the chaperone Hsp90. These observations not only clarify the cellular processes regulating cytosolic access following endocytosis, but also demonstrate that functional proteins can potentially regain their activity in the cytosol of dendritic cells.