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dc.contributor.authorPreissler, Steffenen
dc.contributor.authorRato, Claudiaen
dc.contributor.authorYan, Yahuien
dc.contributor.authorPerera, Lukeen
dc.contributor.authorCzako, Aronen
dc.contributor.authorRon, Daviden
dc.date.accessioned2020-12-11T00:30:29Z
dc.date.available2020-12-11T00:30:29Z
dc.date.issued2020-12-09en
dc.identifier.issn2050-084X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/314982
dc.description.abstractThe metazoan endoplasmic reticulum (ER) serves both as a hub for maturation of secreted proteins and as an intracellular calcium storage compartment, facilitating calcium release-dependent cellular processes. ER calcium depletion robustly activates the unfolded protein response (UPR). However, it is unclear how fluctuations in ER calcium impact organellar proteostasis. Here we report that calcium selectively affects the dynamics of the abundant metazoan ER Hsp70 chaperone BiP, by enhancing its affinity for ADP. In the calcium-replete ER, ADP rebinding to post-ATP hydrolysis BiP-substrate complexes competes with ATP binding during both spontaneous and co-chaperone-assisted nucleotide exchange, favouring substrate retention. Conversely, in the calcium-depleted ER, relative acceleration of ADP-to-ATP exchange favours substrate release. These findings explain the rapid dissociation of certain substrates from BiP observed in the calcium-depleted ER and suggest a mechanism for tuning ER quality control and coupling UPR activity to signals that mobilise ER calcium in secretory cells.
dc.description.sponsorshipWellcome Trust 200848/Z/16/Z
dc.format.mediumElectronicen
dc.languageengen
dc.publishereLife Sciences Publications Ltd
dc.rightsAttribution 4.0 International (CC BY)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleCalcium depletion challenges endoplasmic reticulum proteostasis by destabilising BiP-substrate complexes.en
dc.typeArticle
prism.publicationDate2020en
prism.publicationNameeLifeen
prism.volume9en
dc.identifier.doi10.17863/CAM.62090
dcterms.dateAccepted2020-12-08en
rioxxterms.versionofrecord10.7554/elife.62601en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-12-09en
dc.contributor.orcidPreissler, Steffen [0000-0001-7936-9836]
dc.contributor.orcidRato, Claudia [0000-0002-3971-046X]
dc.contributor.orcidYan, Yahui [0000-0001-6934-9874]
dc.contributor.orcidPerera, Luke [0000-0002-0032-1176]
dc.contributor.orcidCzako, Aron [0000-0002-3220-2083]
dc.contributor.orcidRon, David [0000-0002-3014-5636]
dc.identifier.eissn2050-084X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWELLCOME TRUST (200848/Z/16/Z)
cam.orpheus.successMon Jan 25 12:06:11 GMT 2021 - The item has an open VoR version.*
cam.orpheus.counter1*
rioxxterms.freetoread.startdate2100-01-01


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