Proteostasis in dendritic cells is controlled by the PERK signaling axis independently of ATF4

Andreia Mendes (1, 2) , Julien P Gigan (1) , Christian Rodriguez Rodrigues (1) , Sébastien A Choteau (1, 3) , Doriane Sanseau (4) , Daniela Barros (1, 2) , Catarina Almeida (2) , Voahirana Camosseto (1) , Lionel Chasson (1) , Adrienne W Paton (5) , James C Paton (5) , Rafael J Argüello (1) , Ana-Maria Lennon-Duménil (4) , Evelina Gatti (1, 2) , Philippe Pierre (1, 2)

1 CIML - Centre d'Immunologie de Marseille - Luminy
2 iBiMED - Institute for Research in Biomedicine
3 TAGC - Theories and Approaches of Genomic Complexity
4 U932 - Immunité et cancer
5 University of Adelaide

In stressed cells, phosphorylation of eukaryotic initiation factor 2α (eIF2α) controls transcriptome-wide changes in mRNA translation and gene expression known as the integrated stress response. We show here that DCs are characterized by high eIF2α phosphorylation, mostly caused by the activation of the ER kinase PERK (EIF2AK3). Despite high p-eIF2α levels, DCs display active protein synthesis and no signs of a chronic integrated stress response. This biochemical specificity prevents translation arrest and expression of the transcription factor ATF4 during ER-stress induction by the subtilase cytotoxin (SubAB). PERK inactivation, increases globally protein synthesis levels and regulates IFN-β expression, while impairing LPS-stimulated DC migration. Although the loss of PERK activity does not impact DC development, the cross talk existing between actin cytoskeleton dynamics; PERK and eIF2α phosphorylation is likely important to adapt DC homeostasis to the variations imposed by the immune contexts.

Domaines: Sciences du Vivant [q-bio]

Andreia Mendes, Julien P Gigan, Christian Rodriguez Rodrigues, Sébastien A Choteau, Doriane Sanseau, et al.. Proteostasis in dendritic cells is controlled by the PERK signaling axis independently of ATF4. Life Science Alliance, 2021, 4 (2), pp.e202000865. ⟨10.26508/lsa.202000865⟩. ⟨hal-03121710⟩