{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:18:08Z","timestamp":1792160288413,"version":"4.4.0"},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2010,12,29]],"date-time":"2010-12-29T00:00:00Z","timestamp":1293580800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0015658","type":"journal-article","created":{"date-parts":[[2010,12,30]],"date-time":"2010-12-30T01:27:36Z","timestamp":1293672456000},"page":"e15658","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":73,"title":["Prion Protein Misfolding Affects Calcium Homeostasis and Sensitizes Cells to Endoplasmic Reticulum Stress"],"prefix":"10.1371","volume":"5","author":[{"given":"Mauricio","family":"Torres","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Castillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Armis\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Stutzin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Soto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Hetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2010,12,29]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.2174\/156652408784221324","article-title":"The stress rheostat: an interplay between the unfolded protein response (UPR) and autophagy in neurodegeneration.","volume":"8","author":"S Matus","year":"2008","journal-title":"Curr Mol Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"13363","DOI":"10.1073\/pnas.95.23.13363","article-title":"Prions.","volume":"95","author":"SB Prusiner","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s000180300009","article-title":"Protein misfolding and disease: the case of prion disorders.","volume":"60","author":"C Hetz","year":"2003","journal-title":"Cell Mol Life Sci"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S1471-4914(01)01931-1","article-title":"Prions: disease propagation and disease therapy by conformational transmission.","volume":"7","author":"C Soto","year":"2001","journal-title":"Trends Mol Med"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0166-2236(03)00143-7","article-title":"Prion protein trafficking and the development of neurodegeneration.","volume":"26","author":"RS Hegde","year":"2003","journal-title":"Trends Neurosci"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"5383","DOI":"10.1093\/emboj\/20.19.5383","article-title":"Proteasomes and ubiquitin are involved in the turnover of the wild-type prion protein.","volume":"20","author":"Y Yedidia","year":"2001","journal-title":"Embo J"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"38699","DOI":"10.1074\/jbc.M005543200","article-title":"The chaperone protein BiP binds to a mutant prion protein and mediates its degradation by the proteasome.","volume":"275","author":"T Jin","year":"2000","journal-title":"J Biol Chem"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"14955","DOI":"10.1073\/pnas.011578098","article-title":"Wild-type PrP and a mutant associated with prion disease are subject to retrograde transport and proteasome degradation.","volume":"98","author":"J Ma","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1091\/mbc.12.4.881","article-title":"A transmembrane form of the prion protein contains an uncleaved signal peptide and is retained in the endoplasmic Reticulum.","volume":"12","author":"RS Stewart","year":"2001","journal-title":"Mol Biol Cell"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s12031-007-0023-6","article-title":"Mutant prion protein D202N associated with familial prion disease is retained in the endoplasmic reticulum and forms \u2018curly\u2019 intracellular aggregates.","volume":"32","author":"Y Gu","year":"2007","journal-title":"J Mol Neurosci"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"23396","DOI":"10.1074\/jbc.274.33.23396","article-title":"Proteasomal degradation and N-terminal protease resistance of the codon 145 mutant prion protein.","volume":"274","author":"G Zanusso","year":"1999","journal-title":"J Biol Chem"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2174\/156652406775574578","article-title":"Stressing out the ER: a role of the unfolded protein response in prion-related disorders.","volume":"6","author":"CA Hetz","year":"2006","journal-title":"Curr Mol Med"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"21732","DOI":"10.1074\/jbc.M213247200","article-title":"Mutant PrP is delayed in its exit from the endoplasmic reticulum, but neither wild-type nor mutant PrP undergoes retrotranslocation prior to proteasomal degradation.","volume":"278","author":"B Drisaldi","year":"2003","journal-title":"J Biol Chem"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"28461","DOI":"10.1074\/jbc.272.45.28461","article-title":"Prion protein aggregation reverted by low temperature in transfected cells carrying a prion protein gene mutation.","volume":"272","author":"N Singh","year":"1997","journal-title":"J Biol Chem"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"42409","DOI":"10.1074\/jbc.M106928200","article-title":"Mutant prion proteins are partially retained in the endoplasmic reticulum.","volume":"276","author":"L Ivanova","year":"2001","journal-title":"J Biol Chem"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"3469","DOI":"10.1523\/JNEUROSCI.0105-05.2005","article-title":"Neurodegenerative illness in transgenic mice expressing a transmembrane form of the prion protein.","volume":"25","author":"RS Stewart","year":"2005","journal-title":"J Neurosci"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"15855","DOI":"10.1074\/jbc.M412298200","article-title":"A transmembrane form of the prion protein is localized in the Golgi apparatus of neurons.","volume":"280","author":"RS Stewart","year":"2005","journal-title":"J Biol Chem"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"14945","DOI":"10.1073\/pnas.93.25.14945","article-title":"Subcellular colocalization of the cellular and scrapie prion proteins in caveolae-like membranous domains.","volume":"93","author":"M Vey","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"6324","DOI":"10.1074\/jbc.272.10.6324","article-title":"Characterization of detergent-insoluble complexes containing the cellular prion protein and its scrapie isoform.","volume":"272","author":"N Naslavsky","year":"1997","journal-title":"J Biol Chem"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"25457","DOI":"10.1074\/jbc.M203248200","article-title":"Filipin prevents pathological prion protein accumulation by reducing endocytosis and inducing cellular PrP release.","volume":"277","author":"M Marella","year":"2002","journal-title":"J Biol Chem"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"38972","DOI":"10.1074\/jbc.M205110200","article-title":"Stimulation of PrP(C) retrograde transport toward the endoplasmic reticulum increases accumulation of PrP(Sc) in prion-infected cells.","volume":"277","author":"F Beranger","year":"2002","journal-title":"J Biol Chem"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.devcel.2008.06.015","article-title":"Reduced translocation of nascent prion protein during ER stress contributes to neurodegeneration.","volume":"15","author":"NS Rane","year":"2008","journal-title":"Dev Cell"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1083\/jcb.110.6.2117","article-title":"Scrapie prion proteins accumulate in the cytoplasm of persistently infected cultured cells.","volume":"110","author":"A Taraboulos","year":"1990","journal-title":"J Cell Biol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.molcel.2007.04.001","article-title":"Disease-associated prion protein oligomers inhibit the 26S proteasome.","volume":"26","author":"M Kristiansen","year":"2007","journal-title":"Mol Cell"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1111\/j.1471-4159.2006.03837.x","article-title":"Molecular morphology and toxicity of cytoplasmic prion protein aggregates in neuronal and non-neuronal cells.","volume":"97","author":"C Grenier","year":"2006","journal-title":"J Neurochem"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"38851","DOI":"10.1074\/jbc.M506600200","article-title":"Disease-related prion protein forms aggresomes in neuronal cells leading to caspase activation and apoptosis.","volume":"280","author":"M Kristiansen","year":"2005","journal-title":"J Biol Chem"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1126\/science.1073619","article-title":"Conversion of PrP to a self-perpetuating PrPSc-like conformation in the cytosol.","volume":"298","author":"J Ma","year":"2002","journal-title":"Science"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.molcel.2009.08.021","article-title":"Fine-tuning of the unfolded protein response: Assembling the IRE1alpha interactome.","volume":"35","author":"C Hetz","year":"2009","journal-title":"Mol Cell"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1089\/ars.2007.1793","article-title":"ER stress signaling and the BCL-2 family of proteins: from adaptation to irreversible cellular damage.","volume":"9","author":"CA Hetz","year":"2007","journal-title":"Antioxid Redox Signal"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"5435","DOI":"10.1093\/emboj\/cdg537","article-title":"Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein.","volume":"22","author":"C Hetz","year":"2003","journal-title":"Embo J"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/S0304-3940(02)01071-6","article-title":"Overexpressed protein disulfide isomerase in brains of patients with sporadic Creutzfeldt-Jakob disease.","volume":"334","author":"BC Yoo","year":"2002","journal-title":"Neurosci Lett"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.bbrc.2005.06.060","article-title":"Gene expression profiling of the preclinical scrapie-infected hippocampus.","volume":"334","author":"AR Brown","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1073\/pnas.0711094105","article-title":"Unfolded protein response transcription factor XBP-1 does not influence prion replication or pathogenesis.","volume":"105","author":"C Hetz","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1523\/JNEUROSCI.4090-04.2005","article-title":"The disulfide isomerase Grp58 is a protective factor against prion neurotoxicity.","volume":"25","author":"C Hetz","year":"2005","journal-title":"J Neurosci"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"243","DOI":"10.4161\/pri.1.4.5551","article-title":"Prion pathogenesis is independent of caspase-12.","volume":"1","author":"AD Steele","year":"2007","journal-title":"Prion"},{"key":"ref36","article-title":"Human Prion Protein Mutants with Deleted and Inserted Octarepeats Undergo Different Pathways to Trigger Cell Apoptosis.","author":"K Xu"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"30431","DOI":"10.1074\/jbc.M605320200","article-title":"Conditions of endoplasmic reticulum stress favor the accumulation of cytosolic prion protein.","volume":"281","author":"A Orsi","year":"2006","journal-title":"J Biol Chem"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.bbrc.2006.06.078","article-title":"Cellular tolerance of prion protein PrP in yeast involves proteolysis and the unfolded protein response.","volume":"347","author":"J Apodaca","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.nbd.2006.05.011","article-title":"An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity.","volume":"23","author":"E Ferreiro","year":"2006","journal-title":"Neurobiol Dis"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1111\/j.1471-4159.2007.05048.x","article-title":"Involvement of mitochondria in endoplasmic reticulum stress-induced apoptotic cell death pathway triggered by the prion peptide PrP(106-126).","volume":"104","author":"E Ferreiro","year":"2008","journal-title":"J Neurochem"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1089\/ars.2006.8.1391","article-title":"The endoplasmic reticulum: folding, calcium homeostasis, signaling, and redox control.","volume":"8","author":"A Gorlach","year":"2006","journal-title":"Antioxid Redox Signal"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.arr.2009.05.002","article-title":"The ER and ageing II: calcium homeostasis.","volume":"8","author":"M Puzianowska-Kuznicka","year":"2009","journal-title":"Ageing Res Rev"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0143416002001884","article-title":"Ca2+ signaling and calcium binding chaperones of the endoplasmic reticulum.","volume":"32","author":"M Michalak","year":"2002","journal-title":"Cell Calcium"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/nchembio.368","article-title":"Endoplasmic reticulum Ca2+ increases enhance mutant glucocerebrosidase proteostasis.","volume":"6","author":"DS Ong","journal-title":"Nat Chem Biol"},{"key":"ref45","article-title":"Sarco(endo)plasmic reticulum Ca2+-ATPase 2b is a major regulator of endoplasmic reticulum stress and glucose homeostasis in obesity.","author":"SW Park","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1046\/j.1460-9568.2003.02546.x","article-title":"Involvement of calcineurin in the neurotoxic effects induced by amyloid-beta and prion peptides.","volume":"17","author":"P Agostinho","year":"2003","journal-title":"Eur J Neurosci"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1006\/bbrc.1996.1673","article-title":"Intracellular calcium rise through L-type calcium channels, as molecular mechanism for prion protein fragment 106-126-induced astroglial proliferation.","volume":"228","author":"T Florio","year":"1996","journal-title":"Biochem Biophys Res Commun"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"14077","DOI":"10.1074\/jbc.275.19.14077","article-title":"Alzheimer&apos;s beta-amyloid, human islet amylin, and prion protein fragment evoke intracellular free calcium elevations by a common mechanism in a hypothalamic GnRH neuronal cell line.","volume":"275","author":"M Kawahara","year":"2000","journal-title":"J Biol Chem"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"43516","DOI":"10.1074\/jbc.M103894200","article-title":"Prion protein fragment PrP-(106-126) induces apoptosis via mitochondrial disruption in human neuronal SH-SY5Y cells.","volume":"276","author":"CN O'Donovan","year":"2001","journal-title":"J Biol Chem"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1006\/nbdi.2000.0301","article-title":"Apoptotic cell death and impairment of L-type voltage-sensitive calcium channel activity in rat cerebellar granule cells treated with the prion protein fragment 106-126.","volume":"7","author":"S Thellung","year":"2000","journal-title":"Neurobiol Dis"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.nbd.2008.02.003","article-title":"The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway.","volume":"30","author":"E Ferreiro","year":"2008","journal-title":"Neurobiol Dis"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/47513","article-title":"Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta.","volume":"403","author":"T Nakagawa","year":"2000","journal-title":"Nature"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1126\/science.1081208","article-title":"BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis.","volume":"300","author":"L Scorrano","year":"2003","journal-title":"Science"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"11477","DOI":"10.1074\/jbc.M708385200","article-title":"BI-1 regulates endoplasmic reticulum Ca2+ homeostasis downstream of Bcl-2 family proteins.","volume":"283","author":"C Xu","year":"2008","journal-title":"J Biol Chem"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0143416002001823","article-title":"The endoplasmic reticulum: a multifunctional signaling organelle.","volume":"32","author":"MJ Berridge","year":"2002","journal-title":"Cell Calcium"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1128\/CMR.12.3.429","article-title":"Cellular biology of prion diseases.","volume":"12","author":"DA Harris","year":"1999","journal-title":"Clin Microbiol Rev"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"12725","DOI":"10.1074\/jbc.M611909200","article-title":"Perturbation of endoplasmic reticulum homeostasis facilitates prion replication.","volume":"282","author":"C Hetz","year":"2007","journal-title":"J Biol Chem"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"e1000421","DOI":"10.1371\/journal.ppat.1000421","article-title":"De novo generation of infectious prions in vitro produces a new disease phenotype.","volume":"5","author":"MA Barria","year":"2009","journal-title":"PLoS Pathog"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0896-6273(03)00366-0","article-title":"Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1.","volume":"39","author":"TS Tang","year":"2003","journal-title":"Neuron"},{"key":"ref60","article-title":"Converging pathways in the occurrence of endoplasmic reticulum (ER) stress in Huntington&apos;s disease.","author":"R Vidal","year":"2011","journal-title":"Curr. Mol. Med"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/S0140-6736(99)11419-3","article-title":"Reversion of prion protein conformational changes by synthetic beta-sheet breaker peptides.","volume":"355","author":"C Soto","year":"2000","journal-title":"Lancet"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"4377","DOI":"10.1128\/JVI.74.9.4377-4386.2000","article-title":"Cultured cell sublines highly susceptible to prion infection.","volume":"74","author":"PJ Bosque","year":"2000","journal-title":"J Virol"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"9295","DOI":"10.1073\/pnas.151242598","article-title":"Scrapie prion protein accumulation by scrapie-infected neuroblastoma cells abrogated by exposure to a prion protein antibody.","volume":"98","author":"M Enari","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.ydbio.2004.09.008","article-title":"A mutation in serca underlies motility dysfunction in accordion zebrafish.","volume":"276","author":"MR Gleason","year":"2004","journal-title":"Dev Biol"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1159\/000110437","article-title":"Activation of H2O2-induced VSOR Cl- currents in HTC cells require phospholipase Cgamma1 phosphorylation and Ca2+ mobilisation.","volume":"20","author":"D Varela","year":"2007","journal-title":"Cell Physiol Biochem"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.molcel.2009.02.017","article-title":"BAX inhibitor-1 is a negative regulator of the ER stress sensor IRE1alpha.","volume":"33","author":"F Lisbona","year":"2009","journal-title":"Mol Cell"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0262628","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000}},{"DOI":"10.1371\/annotation\/4087ecad-630d-4436-a301-257b13441156","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2011,3,21]],"date-time":"2011-03-21T00:00:00Z","timestamp":1300665600000}}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0015658","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T10:48:44Z","timestamp":1712054924000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0015658"}},"subtitle":[],"editor":[{"given":"Maria A.","family":"Deli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2010,12,29]]},"references-count":66,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2010,12,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0015658","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,12,29]]}}}