Heat shock protein 90 (HSP90) contributes to cytosolic translocation of extracellular antigen for cross-presentation by dendritic cells

Takashi Imai, Yu Kato, Chiaki Kajiwara, Shusaku Mizukami, Ikuo Ishige, Tomoko Ichiyanagi, Masaki Hikida, Ji Yang Wang, Heiichiro Udono

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

In antigen (Ag) cross-presentation, dendritic cells (DCs) take up extracellular Ag and translocate them from the endosome to the cytosol for proteasomal degradation. The processed peptides can enter the conventional MHC I pathway. The molecules responsible for the translocation of Ag across the endosomal membrane into the cytosol are unknown. Here we demonstrate that heat shock protein 90 (HSP90) is critical for this step. Cross-presentation and -priming were decreased in both HSP90α-null DCs and mice. CD8α + DC apoptosis mediated by translocation of exogenous cytochrome c to the cytosol was also eliminated in HSP90α-null mice. Ag translocation into the cytosol was diminished in HSP90α-null DCs and in DCs treated with an HSP90 inhibitor. Internalized Ag was associated with HSP90 and translocated to the cytosol, a process abrogated by the HSP90 inhibitor. Ag within purified phagosomes was released in an HSP90-dependent manner. These results demonstrate the important role of HSP90 in cross-presentation by pulling endosomal Ag out into the cytosol.

Original languageEnglish
Pages (from-to)16363-16368
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number39
DOIs
Publication statusPublished - Sep 27 2011

Fingerprint

Cross-Priming
HSP90 Heat-Shock Proteins
Antigen Presentation
Dendritic Cells
Cytosol
Antigens
Null Lymphocytes
Phagosomes
Endosomes
Cytochromes c
Apoptosis

Keywords

  • Antigen processing
  • Chaperone
  • Cross-priming
  • Image stream
  • Knock out mouse

ASJC Scopus subject areas

  • General

Cite this

Heat shock protein 90 (HSP90) contributes to cytosolic translocation of extracellular antigen for cross-presentation by dendritic cells. / Imai, Takashi; Kato, Yu; Kajiwara, Chiaki; Mizukami, Shusaku; Ishige, Ikuo; Ichiyanagi, Tomoko; Hikida, Masaki; Wang, Ji Yang; Udono, Heiichiro.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 39, 27.09.2011, p. 16363-16368.

Research output: Contribution to journalArticle

Imai, Takashi ; Kato, Yu ; Kajiwara, Chiaki ; Mizukami, Shusaku ; Ishige, Ikuo ; Ichiyanagi, Tomoko ; Hikida, Masaki ; Wang, Ji Yang ; Udono, Heiichiro. / Heat shock protein 90 (HSP90) contributes to cytosolic translocation of extracellular antigen for cross-presentation by dendritic cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 39. pp. 16363-16368.
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