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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.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.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.titleStress-induced protein disaggregation in the endoplasmic reticulum catalysed by BiP.
dc.publisher.departmentDepartment of Clinical Neurosciences
prism.publicationNameNat Commun
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]
rioxxterms.typeJournal Article/Review
pubs.licence-display-nameApollo Repository Deposit Licence Agreement

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International