ArticleThe Journal of biological chemistry2015
Co-chaperone Specificity in Gating of the Polypeptide Conducting Channel in the Membrane of the Human Endoplasmic Reticulum.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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.
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.
Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Rules of Engagement for Components of Membrane Protein Biogenesis at the Human Endoplasmic Reticulum.International journal of molecular sciences · 2025Review
- Plantamajoside mitigates endoplasmic reticulum stress-mediated pancreatic β-cell apoptosis in type 2 diabetesWorld journal of diabetes · 2025Article
- Hypoaldosteronism due to a novel SEC61A1 variant successfully treated with fludrocortisone.Clinical kidney journal · 2024Article
- Congenital Hyperinsulinism in Humans and Insulin Secretory Dysfunction in Mice Caused by BiallelicInternational journal of molecular sciences · 2024Article
- Sec61γ is a vital protein in the endoplasmic reticulum membrane promoting tumor metastasis and invasion in lung adenocarcinoma.British journal of cancer · 2023Article
- Editorial: The evolving picture of CaFrontiers in physiology · 2023Article
- Regulation of Translation, Translocation, and Degradation of Proteins at the Membrane of the Endoplasmic Reticulum.International journal of molecular sciences · 2022Review
- Sec61 complex/translocon: The role of an atypical ER CaFrontiers in physiology · 2022Review
- Signal Peptide Features Determining the Substrate Specificities of Targeting and Translocation Components in Human ER Protein Import.Frontiers in physiology · 2022Review
- The endoplasmic reticulum membrane protein Sec62 as potential therapeutic target inFrontiers in physiology · 2022Review
- DNAJB11 predicts a poor prognosis and is associated with immune infiltration in thyroid carcinoma: a bioinformatics analysis.The Journal of international medical research · 2021Article
- Complexity and Specificity of Sec61-Channelopathies: Human Diseases Affecting Gating of the Sec61 Complex.Cells · 2021Review
- Intracellular Lipid Accumulation and Mitochondrial Dysfunction Accompanies Endoplasmic Reticulum Stress Caused by Loss of the Co-chaperoneFrontiers in cell and developmental biology · 2021Article
- Characterization of Hailey-Hailey Disease-mutants in presence and absence of wild type SPCA1 using Saccharomyces cerevisiae as model organism.Scientific reports · 2019Article
- Chaperoning Endoplasmic Reticulum-Associated Degradation (ERAD) and Protein Conformational Diseases.Cold Spring Harbor perspectives in biology · 2019Review
- The signal peptide plus a cluster of positive charges in prion protein dictate chaperone-mediated Sec61 channel gating.Biology open · 2019Article
- AXER is an ATP/ADP exchanger in the membrane of the endoplasmic reticulum.Nature communications · 2018Article
- The endoplasmic reticulum HSP40 co-chaperone ERdj3/DNAJB11 assembles and functions as a tetramer.The EMBO journal · 2017Article
- An Update on Sec61 Channel Functions, Mechanisms, and Related Diseases.Frontiers in physiology · 2017Review
- Disruption of Protein Processing in the Endoplasmic Reticulum of DYT1 Knock-in Mice Implicates Novel Pathways in Dystonia Pathogenesis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In mammalian cells, signal peptide-dependent protein transport into the endoplasmic reticulum (ER) is mediated by a dynamic polypeptide-conducting channel, the heterotrimeric Sec61 complex. Previous work has characterized the Sec61 complex as a potential ER Ca(2+) leak channel in HeLa cells and identified ER lumenal molecular chaperone immunoglobulin heavy-chain-binding protein (BiP) as limiting Ca(2+) leakage via the open Sec61 channel by facilitating channel closing. This BiP activity involves binding of BiP to the ER lumenal loop 7 of Sec61α in the vicinity of tyrosine 344. Of note, the Y344H mutation destroys the BiP binding site and causes pancreatic β-cell apoptosis and diabetes in mice. Here, we systematically depleted HeLa cells of the BiP co-chaperones by siRNA-mediated gene silencing and used live cell Ca(2+) imaging to monitor the effects on ER Ca(2+) leakage. Depletion of either one of the ER lumenal BiP co-chaperones, ERj3 and ERj6, but not the ER membrane-resident co-chaperones (such as Sec63 protein, which assists BiP in Sec61 channel opening) led to increased Ca(2+) leakage via Sec6 complex, thereby phenocopying the effect of BiP depletion. Thus, BiP facilitates Sec61 channel closure (i.e. limits ER Ca(2+) leakage) via the Sec61 channel with the help of ERj3 and ERj6. Interestingly, deletion of ERj6 causes pancreatic β-cell failure and diabetes in mice and humans. We suggest that co-chaperone-controlled gating of the Sec61 channel by BiP is particularly important for cells, which are highly active in protein secretion, and that breakdown of this regulatory mechanism can cause apoptosis and disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.