Lysyl tRNA synthetase is required for the translocation of calreticulin to the cell surface in immunogenic death

Oliver Kepp, Abdelaziz Gdoura, Isabelle Martins, Theocharis Panaretakis, Frederic Schlemmer, Antoine Tesniere, Gian Maria Fimia, Fabiola Ciccosanti, Anne Burgevin, Mauro Piacentini, Paul Eggleton, Philip J. Young, Laurence Zitvogel, Peter Van Endert, Guido Kroemer

Research output: Contribution to journalArticlepeer-review

Abstract

In response to immunogenic cell death inducers, calreticulin (CRT) translocates from its orthotopic localization in the lumen of the endoplasmic reticulum (ER) to the surface of the plasma membrane where it serves as an engulfment signal for antigen-presenting cells.1 Here, we report that yet another ER protein, the lysyl-tRNA synthetase (KARS), was exposed on the surface of stressed cells, on which KARS co-localized with CRT in lipid rafts. Depletion of KARS with small interfering RNAs suppressed CRT exposure induced by anthracyclines or UVC light. In contrast to CRT, KARS was also found in the supernatant of stressed cells. Recombinant KARS protein was unable to influence the binding of recombinant CRT to the cell surface. Moreover, recombinant KARS protein was unable to stimulate macrophages in vitro. These results underscore the contribution of KARS to the emission of (one of) the principal signal(s) of immunogenic cell death, CRT exposure.

Original languageEnglish
Pages (from-to)3072-3077
Number of pages6
JournalCell Cycle
Volume9
Issue number15
DOIs
Publication statusPublished - Aug 1 2010

Keywords

  • Anthracyclines
  • Apoptosis
  • Calreticulin receptor
  • ER stress

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

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