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dc.contributor.authorMelo, Eduardo Pinho
dc.contributor.authorKonno, Tasuku
dc.contributor.authorFarace, Ilaria
dc.contributor.authorAwadelkareem, Mosab Ali
dc.contributor.authorSkov, Lise R
dc.contributor.authorTeodoro, Fernando
dc.contributor.authorSancho, Teresa P
dc.contributor.authorPaton, Adrienne W
dc.contributor.authorPaton, James C
dc.contributor.authorFares, Matthew
dc.contributor.authorPaulo, Pedro MR
dc.contributor.authorZhang, Xin
dc.contributor.authorAvezov, Edward
dc.date.accessioned2022-05-09T11:03:55Z
dc.date.available2022-05-09T11:03:55Z
dc.date.issued2022-05-06
dc.date.submitted2021-05-21
dc.identifier.others41467-022-30238-2
dc.identifier.other30238
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336894
dc.descriptionFunder: This study received Portuguese national funds from FCT - Foundation for Science and Technology through project UIDB/04326/2020, UIDP/04326/2020 and LA/P70101/2020, and from the operational programmes CRESC Algarve 2020 and COMPETE 2020 through project EMBRC.PT ALG-01-0145-FEDER-022121
dc.descriptionFunder: UK Medical Research Council
dc.description.abstractAbstract: Protein synthesis is supported by cellular machineries that ensure polypeptides fold to their native conformation, whilst eliminating misfolded, aggregation prone species. Protein aggregation underlies pathologies including neurodegeneration. Aggregates’ formation is antagonised by molecular chaperones, with cytoplasmic machinery resolving insoluble protein aggregates. However, it is unknown whether an analogous disaggregation system exists in the Endoplasmic Reticulum (ER) where ~30% of the proteome is synthesised. Here we show that the ER of a variety of mammalian cell types, including neurons, is endowed with the capability to resolve protein aggregates under stress. Utilising a purpose-developed protein aggregation probing system with a sub-organellar resolution, we observe steady-state aggregate accumulation in the ER. Pharmacological induction of ER stress does not augment aggregates, but rather stimulate their clearance within hours. We show that this dissagregation activity is catalysed by the stress-responsive ER molecular chaperone – BiP. This work reveals a hitherto unknow, non-redundant strand of the proteostasis-restorative ER stress response.
dc.languageen
dc.publisherNature Publishing Group UK
dc.subjectArticle
dc.subject/631/80/304
dc.subject/631/80/470/1981
dc.subject/631/80/470/1463
dc.subject/631/80/470/2284
dc.subject/9
dc.subject/13
dc.subject/13/31
dc.subject/13/100
dc.subject/13/106
dc.subject/13/109
dc.subject/14
dc.subject/14/19
dc.subject/14/34
dc.subject/14/63
dc.subject/38/88
dc.subject/82/16
dc.subjectarticle
dc.titleStress-induced protein disaggregation in the endoplasmic reticulum catalysed by BiP
dc.typeArticle
dc.date.updated2022-05-09T11:03:55Z
prism.issueIdentifier1
prism.publicationNameNature Communications
prism.volume13
dc.identifier.doi10.17863/CAM.84313
dcterms.dateAccepted2022-04-20
rioxxterms.versionofrecord10.1038/s41467-022-30238-2
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidMelo, Eduardo Pinho [0000-0002-0974-8977]
dc.contributor.orcidKonno, Tasuku [0000-0002-4983-5805]
dc.contributor.orcidAwadelkareem, Mosab Ali [0000-0001-6898-6310]
dc.contributor.orcidSkov, Lise R. [0000-0002-7142-7728]
dc.contributor.orcidTeodoro, Fernando [0000-0001-5384-1469]
dc.contributor.orcidPaton, James C. [0000-0001-9807-5278]
dc.contributor.orcidZhang, Xin [0000-0001-6686-1645]
dc.contributor.orcidAvezov, Edward [0000-0002-2894-0585]
dc.identifier.eissn2041-1723
pubs.funder-project-idAlzheimer's Society (AS-595)


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