Evidence map›Paper›PMID 25575667›Full record

ArticleBMC biology2015

Retarded PDI diffusion and a reductive shift in poise of the calcium depleted endoplasmic reticulum.

Edward Avezov, Tasuku Konno, Alisa Zyryanova, Weiyue Chen, Romain Laine, Ana Crespillo-Casado, Eduardo Pinho Melo, Ryo Ushioda, Kazuhiro Nagata, Clemens F Kaminski and 2 more

Open access · goldAbstract read
In one paragraph

Article in BMC biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.7field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
  2. Oxidative protein folding and CaCellular and molecular life sciences : CMLS · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. A View of the Endoplasmic Reticulum Through the Calreticulin Lens.Progress in molecular and subcellular biology · 2021
    Article
  16. Article
  17. CaBMC biology · 2020
    Article
  18. Reductive Stress-Induced Mitochondrial Dysfunction and Cardiomyopathy.Oxidative medicine and cellular longevity · 2020
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 3 countries.

Edward AvezovUniversity of Cambridge, Cambridge Institute for Medical Research, Biomedical Campus, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, United Kingdom. ea347@cam.ac.uk.
Tasuku KonnoUniversity of Cambridge, Cambridge Institute for Medical Research, Biomedical Campus, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, United Kingdom. tk431@medschl.cam.ac.uk.
Alisa ZyryanovaUniversity of Cambridge, Cambridge Institute for Medical Research, Biomedical Campus, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, United Kingdom. az310@cam.ac.uk.
Weiyue ChenDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB2 3RA, UK. wc269@cam.ac.uk.
Romain LaineDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB2 3RA, UK. rfl30@cam.ac.uk.
Ana Crespillo-CasadoUniversity of Cambridge, Cambridge Institute for Medical Research, Biomedical Campus, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, United Kingdom. ac880@cam.ac.uk.
Eduardo Pinho MeloCenter for Biomedical Research, Universidade do Algarve, Faro, Portugal. emelo@ualg.pt.
Ryo UshiodaFaculty of Life Sciences, Kyoto Sangyo University, Kita-Ku, Kyoto-City, 603-8555, Japan. ryo3ussy3@cc.kyoto-su.ac.jp.
Kazuhiro NagataFaculty of Life Sciences, Kyoto Sangyo University, Kita-Ku, Kyoto-City, 603-8555, Japan. nagata@cc.kyoto-su.ac.jp.
Clemens F KaminskiDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB2 3RA, UK. cfk23@cam.ac.uk.
Heather P HardingUniversity of Cambridge, Cambridge Institute for Medical Research, Biomedical Campus, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, United Kingdom. hph23@cam.ac.uk.
David RonUniversity of Cambridge, Cambridge Institute for Medical Research, Biomedical Campus, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, United Kingdom. dr360@medschl.cam.ac.uk.
University of Cambridge · GBKyoto Sangyo University · JPUniversity of Algarve · PT

Funding

Wellcome Trust 084812Wellcome Trust 084812/Z/08/ZWellcome Trust 100140
6 · The paper itself

Abstract

backgroundEndoplasmic reticulum (ER) lumenal protein thiol redox balance resists dramatic variation in unfolded protein load imposed by diverse physiological challenges including compromise in the key upstream oxidases. Lumenal calcium depletion, incurred during normal cell signaling, stands out as a notable exception to this resilience, promoting a rapid and reversible shift towards a more reducing poise. Calcium depletion induced ER redox alterations are relevant to physiological conditions associated with calcium signaling, such as the response of pancreatic cells to secretagogues and neuronal activity. The core components of the ER redox machinery are well characterized; however, the molecular basis for the calcium-depletion induced shift in redox balance is presently obscure.

resultsIn vitro, the core machinery for generating disulfides, consisting of ERO1 and the oxidizing protein disulfide isomerase, PDI1A, was indifferent to variation in calcium concentration within the physiological range. However, ER calcium depletion in vivo led to a selective 2.5-fold decline in PDI1A mobility, whereas the mobility of the reducing PDI family member, ERdj5 was unaffected. In vivo, fluorescence resonance energy transfer measurements revealed that declining PDI1A mobility correlated with formation of a complex with the abundant ER chaperone calreticulin, whose mobility was also inhibited by calcium depletion and the calcium depletion-mediated reductive shift was attenuated in cells lacking calreticulin. Measurements with purified proteins confirmed that the PDI1A-calreticulin complex dissociated as Ca(2+) concentrations approached those normally found in the ER lumen ([Ca(2+)]K(0.5max) = 190 μM).

conclusionsOur findings suggest that selective sequestration of PDI1A in a calcium depletion-mediated complex with the abundant chaperone calreticulin attenuates the effective concentration of this major lumenal thiol oxidant, providing a plausible and simple mechanism for the observed shift in ER lumenal redox poise upon physiological calcium depletion.

Indexed as

DiffusionAnimalsCalciumCalreticulinChlorocebus aethiopsCOS CellsDisulfidesEndoplasmic ReticulumHEK293 CellsHSP40 Heat-Shock ProteinsHumansMiceMolecular ChaperonesOxidation-ReductionProtein BindingProtein Disulfide-IsomerasesCalciumCalreticulinDisulfidesDNAJC10 protein, humanHSP40 Heat-Shock ProteinsMolecular ChaperonesProtein Disulfide-Isomerases

Identifiers

PMID25575667
PMCPMC4316587
OpenAlexW1976094206

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.