title: Lysyl tRNA synthetase is required for the translocation of calreticulin to the cell surface in immunogenic death.
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.
authors.affiliation: INSERM, U848, Villejuif, France.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kepp
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Gdoura
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martins
authors.forename: Theocharis
authors.initials: T
authors.lastname: Panaretakis
authors.forename: Frederic
authors.initials: F
authors.lastname: Schlemmer
authors.forename: Antoine
authors.initials: A
authors.lastname: Tesniere
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Fimia
authors.forename: Fabiola
authors.initials: F
authors.lastname: Ciccosanti
authors.forename: Anne
authors.initials: A
authors.lastname: Burgevin
authors.forename: Mauro
authors.initials: M
authors.lastname: Piacentini
authors.forename: Paul
authors.initials: P
authors.lastname: Eggleton
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Young
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Peter
authors.initials: P
authors.lastname: van Endert
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000595:Amino Acid Sequence; D018943:Anthracyclines / Q000494:pharmacology; D037282:Calreticulin / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008250:Lysine-tRNA Ligase / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018943:Anthracyclines; D037282:Calreticulin; D008250:Lysine-tRNA Ligase