2026-04-18T05:59:33Zhttps://recercat.cat/oai/requestoai:recercat.cat:10230/421952025-12-12T03:23:21Zcom_2072_6col_2072_452952
RECERCAT
author
Chiritoiu, Marioara
author
Brouwers, Nathalie
author
Turacchio, Gabriele
author
Pirozzi, Marianella
author
Malhotra, Vivek
2019-07-29T06:13:35Z2019
Signal-sequence-lacking interleukin (IL)-1β, is cleaved by caspase-1 to mature mIL-1β, which is secreted, without entering the endoplasmic reticulum. We report that macrophages of GRASP55-/- mice are defective in mIL-1β secretion and retain it as intracellular aggregates. Intriguingly, GRASP55-/- macrophages are defective in the IRE1α branch of the unfolded protein response. This finding fits well with our data that inhibition of IRE1α also impairs mIL-1β secretion and causes its accumulation in intracellular aggregates. PERK inhibition, on the other hand, controls caspase-1-mediated conversion of proIL-1β to mIL-1β. These findings reveal translation-independent functions of PERK and IRE1α: PERK controls the production of mIL-1β, which is then followed by GRASP55 and IRE1α activity to keep mIL-1β in a secretion-competent form.This work was funded by grants from the Spanish Ministry of Economy and Competitiveness (BFU2013-44188-P and BFU2016_75372-P to V.M.). We acknowledge support of the Spanish Ministry of Economy and Competitiveness, through the Programmes “Centro de Excelencia Severo Ochoa 2013- 2017” (SEV-2012-0208 and SEV-2013-0347).
© Elsevier http://dx.doi.org/10.1016/j.devcel.2019.02.011 info:eu-repo/semantics/openAccess
GRASP
Interleukin-1β (IL-1β)
Unconventional protein secretion (UPS)
Unfolded protein response (UPR)
GRASP55 and UPR control interleukin-1β aggregation and secretion
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion