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Rhomboid intramembrane protease RHBDL4 triggers ER-export and non-canonical secretion of membrane-anchored TGFα

dc.contributor.authorWunderle, Lina
dc.contributor.authorKnopf, Julia D.
dc.contributor.authorKühnle, Nathalie
dc.contributor.authorMorlé, Aymeric
dc.contributor.authorHehn, Beate
dc.contributor.authorAdrain, Colin
dc.contributor.authorStrisovsky, Kvido
dc.contributor.authorFreeman, Matthew
dc.contributor.authorLemberg, Marius K.
dc.date.accessioned2016-06-13T12:11:48Z
dc.date.available2016-06-13T12:11:48Z
dc.date.issued2016-06-06
dc.description.abstractRhomboid intramembrane proteases are the enzymes that release active epidermal growth factor receptor (EGFR) ligands in Drosophila and C. elegans, but little is known about their functions in mammals. Here we show that the mammalian rhomboid protease RHBDL4 (also known as Rhbdd1) promotes trafficking of several membrane proteins, including the EGFR ligand TGFα, from the endoplasmic reticulum (ER) to the Golgi apparatus, thereby triggering their secretion by extracellular microvesicles. Our data also demonstrate that RHBDL4-dependent trafficking control is regulated by G-protein coupled receptors, suggesting a role for this rhomboid protease in pathological conditions, including EGFR signaling. We propose that RHBDL4 reorganizes trafficking events within the early secretory pathway in response to GPCR signaling. Our work identifies RHBDL4 as a rheostat that tunes secretion dynamics and abundance of specific membrane protein cargoes.pt_PT
dc.description.sponsorshipBaden-Württemberg Stiftung; Network of Aging Research (NAR, University of Heidelberg); Deutsche Forschungsgemeinschaft grant: (SFB 1036, TP 12); EMBO Installation Grant number: (2329); Ministry of Education, Youth and Sports of the Czech Republic projects: (LK11206, LO1302); Medical Research Council programme number: (U105178780); Boehringer-Ingelheim.pt_PT
dc.identifier.citationWunderle, L. et al. Rhomboid intramembrane protease RHBDL4 triggers ER-export and non-canonical secretion of membrane-anchored TGFα. Sci. Rep. 6 , 27342; doi: 10.1038/srep27342 (2016).pt_PT
dc.identifier.doi10.1038/srep27342pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/640
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNature Publishing Grouppt_PT
dc.relation.publisherversionhttp://www.nature.com/articles/srep27342pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectRHBDL4pt_PT
dc.subjectTGFαpt_PT
dc.subjectendoplasmic reticulumpt_PT
dc.subjectrhomboid proteasept_PT
dc.titleRhomboid intramembrane protease RHBDL4 triggers ER-export and non-canonical secretion of membrane-anchored TGFαpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/WT/101035
oaire.citation.endPage15pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleScientific Reportspt_PT
oaire.citation.volume6pt_PT
oaire.fundingStream101035
project.funder.identifierhttp://doi.org/10.13039/100010269
project.funder.nameWellcome Trust
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationf649c65b-9d7f-4f06-b843-2e55c4a763fa
relation.isProjectOfPublication.latestForDiscoveryf649c65b-9d7f-4f06-b843-2e55c4a763fa

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