Calreticulin-dependent recycling in the early secretory pathway mediates optimal peptide loading of MHC class i molecules

Christopher Howe, Malgorzata Garstka, Mohammed Al-Balushi, Esther Ghanem, Antony N. Antoniou, Susanne Fritzsche, Gytis Jankevicius, Nasia Kontouli, Clemens Schneeweiss, Anthony Williams, Tim Elliott, Sebastian Springer

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Calreticulin is a lectin chaperone of the endoplasmic reticulum (ER). In calreticulin-deficient cells, major histocompatibility complex (MHC) class I molecules travel to the cell surface in association with a sub-optimal peptide load. Here, we show that calreticulin exits the ER to accumulate in the ER-Golgi intermediate compartment (ERGIC) and the cis-Golgi, together with sub-optimally loaded class I molecules. Calreticulin that lacks its C-terminal KDEL retrieval sequence assembles with the peptide-loading complex but neither retrieves sub-optimally loaded class I molecules from the cis-Golgi to the ER, nor supports optimal peptide loading. Our study, to the best of our knowledge, demonstrates for the first time a functional role of intracellular transport in the optimal loading of MHC class I molecules with antigenic peptide.

Original languageEnglish
Pages (from-to)3730-3744
Number of pages15
JournalEMBO Journal
Volume28
Issue number23
DOIs
Publication statusPublished - Dec 2009

Fingerprint

Calreticulin
Secretory Pathway
Recycling
Major Histocompatibility Complex
Endoplasmic Reticulum
Peptides
Molecules
lysyl-aspartyl-glutamyl-leucine
Lectins

Keywords

  • Calreticulin
  • Endoplasmic reticulum
  • Major histocompatibility complex (MHC) class I molecules
  • Peptides
  • Quality control

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Calreticulin-dependent recycling in the early secretory pathway mediates optimal peptide loading of MHC class i molecules. / Howe, Christopher; Garstka, Malgorzata; Al-Balushi, Mohammed; Ghanem, Esther; Antoniou, Antony N.; Fritzsche, Susanne; Jankevicius, Gytis; Kontouli, Nasia; Schneeweiss, Clemens; Williams, Anthony; Elliott, Tim; Springer, Sebastian.

In: EMBO Journal, Vol. 28, No. 23, 12.2009, p. 3730-3744.

Research output: Contribution to journalArticle

Howe, C, Garstka, M, Al-Balushi, M, Ghanem, E, Antoniou, AN, Fritzsche, S, Jankevicius, G, Kontouli, N, Schneeweiss, C, Williams, A, Elliott, T & Springer, S 2009, 'Calreticulin-dependent recycling in the early secretory pathway mediates optimal peptide loading of MHC class i molecules', EMBO Journal, vol. 28, no. 23, pp. 3730-3744. https://doi.org/10.1038/emboj.2009.296
Howe, Christopher ; Garstka, Malgorzata ; Al-Balushi, Mohammed ; Ghanem, Esther ; Antoniou, Antony N. ; Fritzsche, Susanne ; Jankevicius, Gytis ; Kontouli, Nasia ; Schneeweiss, Clemens ; Williams, Anthony ; Elliott, Tim ; Springer, Sebastian. / Calreticulin-dependent recycling in the early secretory pathway mediates optimal peptide loading of MHC class i molecules. In: EMBO Journal. 2009 ; Vol. 28, No. 23. pp. 3730-3744.
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