2026-04-14T08:05:29Zhttps://recercat.cat/oai/request

oai:recercat.cat:10230/421952025-12-12T03:23:21Zcom_2072_6col_2072_452952

GRASP55 and UPR control interleukin-1β aggregation and secretion Chiritoiu, Marioara Brouwers, Nathalie Turacchio, Gabriele Pirozzi, Marianella Malhotra, Vivek GRASP Interleukin-1β (IL-1β) Unconventional protein secretion (UPS) Unfolded protein response (UPR) 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). 2019-07-29T06:13:35Z 2019 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Developmental Cell. 2019;49(1):145-55 info:eu-repo/grantAgreement/ES/1PE/BFU2013-44188-P info:eu-repo/grantAgreement/ES/1PE/BFU2016_75372-P © Elsevier http://dx.doi.org/10.1016/j.devcel.2019.02.011 info:eu-repo/semantics/openAccess Elsevier