Lysyl tRNA synthetase is required for the translocation of calreticulin to the cell surface in immunogenic death.
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.
Kepp
Oliver
O
INSERM, U848, Villejuif, France.
Gdoura
Abdelaziz
A
Martins
Isabelle
I
Panaretakis
Theocharis
T
Schlemmer
Frederic
F
Tesniere
Antoine
A
Fimia
Gian Maria
GM
Ciccosanti
Fabiola
F
Burgevin
Anne
A
Piacentini
Mauro
M
Eggleton
Paul
P
Young
Philip J
PJ
Zitvogel
Laurence
L
van Endert
Peter
P
Kroemer
Guido
G
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
D018943:Anthracyclines; D037282:Calreticulin; D008250:Lysine-tRNA Ligase