Interplay between the oxidoreductase pdia6 and microrna-322 controls the response to disrupted endoplasmic reticulum calcium homeostasis

SCIENCE SIGNALING;
Sci. Signal.

dc.creatorGroenendyk, Jody
dc.creatorPeng, Zhenling L.
dc.creatorDudek, Elzbieta
dc.creatorFan, Xiao
dc.creatorMizianty, Marcin J.
dc.creatorDufey, Estefanie
dc.creatorUrra, Hery
dc.creatorSepulveda, Denisse
dc.creatorRojas-Rivera, Diego
dc.creatorLim, Yunki
dc.creatorKim, Do Han
dc.creatorBaretta, Kayla
dc.creatorSrikanth, Sonal
dc.creatorGwack, Yousang
dc.creatorAhnn, Joohong
dc.creatorKaufman, Randal J.
dc.creatorLee, Sun-Kyung
dc.creatorHetz-Flores, Claudio Andres
dc.creatorKurgan, Lukasz
dc.creatorMichalak, Marek
dc.date2017-04-27T18:50:19Z
dc.date2022-07-07T02:19:19Z
dc.date2017-04-27T18:50:19Z
dc.date2022-07-07T02:19:19Z
dc.date2014
dc.date.accessioned2023-08-22T03:06:00Z
dc.date.available2023-08-22T03:06:00Z
dc.identifier1937-9145
dc.identifierD11I1007
dc.identifierD11I1007
dc.identifierWOS:000337179100002
dc.identifier1945-0877
dc.identifierhttps://hdl.handle.net/10533/197085
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8313394
dc.descriptionThe disruption of the energy or nutrient balance triggers endoplasmic reticulum (ER) stress, a process that mobilizes various strategies, collectively called the unfolded protein response (UPR), which reestablish homeostasis of the ER and cell. Activation of the UPR stress sensor IRE1 alpha (inositol-requiring enzyme 1 alpha) stimulates its endoribonuclease activity, leading to the generation of the mRNA encoding the transcription factor XBP1 (X-box binding protein 1), which regulates the transcription of genes encoding factors involved in controlling the quality and folding of proteins. We found that the activity of IRE1 alpha was regulated by the ER oxidoreductase PDIA6 (protein disulfide isomerase A6) and the microRNA miR-322 in response to disruption of ER Ca2+ homeostasis. PDIA6 interacted with IRE1 alpha and enhanced IRE1 alpha activity as monitored by phosphorylation of IRE1 alpha and XBP1 mRNA splicing, but PDIA6 did not substantially affect the activity of other pathways that mediate responses to ER stress. ER Ca2+ depletion and activation of store-operated Ca2+ entry reduced the abundance of the microRNA miR-322, which increased PDIA6 mRNA stability and, consequently, IRE1 alpha activity during the ER stress response. In vivo experiments with mice and worms showed that the induction of ER stress correlated with decreased miR-322 abundance, increased PDIA6 mRNA abundance, or both. Together, these findings demonstrated that ER Ca2+, PDIA6, IRE1 alpha, and miR-322 function in a dynamic feedback loop modulating the UPR under conditions of disrupted ER Ca2+ homeostasis.
dc.descriptionSupported by the Canadian Institutes of Health Research grants MOP-15291, MOP-15415, and MOP-53050 to M. M.; NIH grants DK042394, DK088227, HL052173, and HL057346 to R.J.K.; NIH grant AI083432 to Y.G.; the American Heart Association (12SDG12040188) to S. S.; FONDEF D11I1007, Ring Initiative ACT1109; Millennium Institute No. P09-015-F, the Alzheimer's Association FONDECYT No. 1140549, ECOS CONICYT C13S02, the Muscular Dystrophy Association, ALS Therapy Alliance, and CONICYT-EEUU collaboration grant USA2013-0003 to C.H.; FONDECYT No. 3130365 postdoctoral grant to D.R.-R.; CONICYT PhD fellowships to E. Dufey, H.U., and D.S.; 2013 GIST Systems Biology Infrastructure Establishment Grant to D.H.K.; Korean Ministry of Science, ICT, and Future Planning (the Women Scientist program, 2013R1A1A3A04006010) to S.-K.L.; Korean Ministry of Education (Basic Science Research Program 2013R1A1A2005836) to J.A.; Alberta Innovates-Health Solutions graduate student scholarship to Z.P.; Dissertation Fellowship from University of Alberta to M.J.M.; and Alberta Innovates-Health Solutions postdoctoral fellowship to E. Dudek.
dc.description16
dc.descriptionFONDEF
dc.descriptionmarek.michalak@ualberta.ca
dc.descriptionCanadian Institutes of Health Research [MOP-15291, MOP-15415, MOP-53050]; NIH [DK042394, DK088227, HL052173, HL057346, AI083432]; American Heart Association [12SDG12040188]; FONDEF [D11I1007]; Ring Initiative ACT1109; Millennium Institute [P09-015-F]; Alzheimer's Association FONDECYT [1140549]; ECOS CONICYT [C13S02]; Muscular Dystrophy Association; ALS Therapy Alliance; CONICYT-EEUU [USA2013-0003]; FONDECYT [3130365]; CONICYT PhD fellowships; GIST Systems Biology Infrastructure Establishment Grant; Korean Ministry of Science, ICT, and Future Planning (the Women Scientist program) [2013R1A1A3A04006010]; Korean Ministry of Education (Basic Science Research Program) [2013R1A1A2005836]; Alberta Innovates-Health Solutions graduate student scholarship; Dissertation Fellowship from University of Alberta; Alberta Innovates-Health Solutions postdoctoral fellowship
dc.descriptionFONDEF
dc.languageENG
dc.publisherAMER ASSOC ADVANCEMENT SCIENCE
dc.relationinstname: Conicyt
dc.relationreponame: Repositorio Digital RI2.0
dc.relationinstname: Conicyt
dc.relationreponame: Repositorio Digital RI2.0
dc.relationinfo:eu-repo/grantAgreement/Fondef/D11I1007
dc.relationinfo:eu-repo/semantics/dataset/hdl.handle.net/10533/93477
dc.relationhttps://doi.org/10.1126/scisignal.2004983
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleInterplay between the oxidoreductase pdia6 and microrna-322 controls the response to disrupted endoplasmic reticulum calcium homeostasis
dc.titleSCIENCE SIGNALING
dc.titleSci. Signal.
dc.typeArticulo
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.coverageWASHINGTON


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