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Stress-induced protein disaggregation in the endoplasmic reticulum catalysed by BiP.

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cam.issuedOnline2022-05-06
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.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.date.accessioned2022-06-07T08:17:09Z
dc.date.available2022-06-07T08:17:09Z
dc.date.issued2022-05-06
dc.date.updated2022-06-07T08:17:08Z
dc.description.abstractProtein 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.identifier.doi10.17863/CAM.85255
dc.identifier.eissn2041-1723
dc.identifier.issn2041-1723
dc.identifier.other35523806
dc.identifier.otherPMC9076838
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337846
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/s41467-022-30238-2
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101528555
dc.sourceessn: 2041-1723
dc.subjectAnimals
dc.subjectEndoplasmic Reticulum
dc.subjectEndoplasmic Reticulum Chaperone BiP
dc.subjectEndoplasmic Reticulum Stress
dc.subjectMammals
dc.subjectMolecular Chaperones
dc.subjectProtein Aggregates
dc.titleStress-induced protein disaggregation in the endoplasmic reticulum catalysed by BiP.
dc.typeArticle
dcterms.dateAccepted2022-04-20
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume13
pubs.funder-project-idAlzheimer's Society (595, AS-595)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41467-022-30238-2

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