GRASP55 and UPR control interleukin-1β aggregation and secretion

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• dc.contributor.author Chiritoiu, Marioara
• dc.contributor.author Brouwers, Nathalie
• dc.contributor.author Turacchio, Gabriele
• dc.contributor.author Pirozzi, Marianella
• dc.contributor.author Malhotra, Vivek
• dc.date.accessioned 2019-07-29T06:13:35Z
• dc.date.issued 2019
• dc.description.abstract 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.
• dc.description.sponsorship 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).
• dc.format.mimetype application/pdf
• dc.identifier.citation Chiritoiu M, Brouwers N, Turacchio G, Pirozzi M, Malhotra V. GRASP55 and UPR control interleukin-1β aggregation and secretion. Dev Cell. 2019;49(1):145-55. DOI: 10.1016/j.devcel.2019.02.011
• dc.identifier.doi http://dx.doi.org/10.1016/j.devcel.2019.02.011
• dc.identifier.issn 1534-5807
• dc.identifier.uri http://hdl.handle.net/10230/42195
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Developmental Cell. 2019;49(1):145-55
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2013-44188-P
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2016_75372-P
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.devcel.2019.02.011
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword GRASP
• dc.subject.keyword Interleukin-1β (IL-1β)
• dc.subject.keyword Unconventional protein secretion (UPS)
• dc.subject.keyword Unfolded protein response (UPR)
• dc.title GRASP55 and UPR control interleukin-1β aggregation and secretion
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion