ArticleMolecular biology of the cell2013
Ubiquitination-dependent quality control of hERG K+ channel with acquired and inherited conformational defect at the plasma membrane.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 46 citations in OpenAlex.
- Quantitative analysis of trafficking defects induced by heterozygous expression of hERG voltage sensor domain variants.Channels (Austin, Tex.) · 2026Article
- α-mannosidase I-dependent N-linked glycosylation affects hERG channel functional availability during reactivation.The journal of physiological sciences : JPS · 2026Article
- Computational modelling of the pro- and antiarrhythmic effects of atrial high rate-dependent trafficking of small-conductance calcium-activated potassium channels.The Journal of physiology · 2026Article
- A privileged ER compartment for posttranslational heteromeric assembly of an ion channel.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A privileged ER compartment for post-translational heteromeric assembly of an ion channel.bioRxiv : the preprint server for biology · 2025Article
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
- The proteostasis interactomes of trafficking-deficient variants of the voltage-gated potassium channel KThe Journal of biological chemistry · 2024Article
- Ligand-based virtual-screening identified a novel CFTR ligand which improves the defective cell surface expression of misfolded ABC transporters.Frontiers in pharmacology · 2024Article
- In silico analysis of the dynamic regulation of cardiac electrophysiology by KThe Journal of physiology · 2023Article
- The cellular pathways that maintain the quality control and transport of diverse potassium channels.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
- DNA topoisomerase 2-associated proteins PATL1 and PATL2 regulate the biogenesis of hERG KProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Ubr1-induced selective endophagy/autophagy protects against the endosomal and CaCellular and molecular life sciences : CMLS · 2022Article
- Volleying plasma membrane proteins from birth to death: Role of J-domain proteins.Frontiers in molecular biosciences · 2022Review
- Evolutionary coupling analysis guides identification of mistrafficking-sensitive variants in cardiac KFrontiers in pharmacology · 2022Article
- Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations.Scientific reports · 2021Article
- Modified N-linked glycosylation status predicts trafficking defective human Piezo1 channel mutations.Communications biology · 2021Article
- Toward a broader view of mechanisms of drug cardiotoxicity.Cell reports. Medicine · 2021Review
- Serine mutation of a conserved threonine in the hERG KBiochemical and biophysical research communications · 2020Article
- Structures Illuminate Cardiac Ion Channel Functions in Health and in Long QT Syndrome.Frontiers in pharmacology · 2020Review
- Misfolded GPI-anchored proteins are escorted through the secretory pathway by ER-derived factors.eLife · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Membrane trafficking in concert with the peripheral quality control machinery plays a critical role in preserving plasma membrane (PM) protein homeostasis. Unfortunately, the peripheral quality control may also dispose of partially or transiently unfolded polypeptides and thereby contribute to the loss-of-expression phenotype of conformational diseases. Defective functional PM expression of the human ether-a-go-go-related gene (hERG) K(+) channel leads to the prolongation of the ventricular action potential that causes long QT syndrome 2 (LQT2), with increased propensity for arrhythmia and sudden cardiac arrest. LQT2 syndrome is attributed to channel biosynthetic processing defects due to mutation, drug-induced misfolding, or direct channel blockade. Here we provide evidence that a peripheral quality control mechanism can contribute to development of the LQT2 syndrome. We show that PM hERG structural and metabolic stability is compromised by the reduction of extracellular or intracellular K(+) concentration. Cardiac glycoside-induced intracellular K(+) depletion conformationally impairs the complex-glycosylated channel, which provokes chaperone- and C-terminal Hsp70-interacting protein-dependent polyubiquitination, accelerated internalization, and endosomal sorting complex required for transport-dependent lysosomal degradation. A similar mechanism contributes to the down-regulation of PM hERG harboring LQT2 missense mutations, with incomplete secretion defect. These results suggest that PM quality control plays a determining role in the loss-of-expression phenotype of hERG in certain hereditary and acquired LTQ2 syndromes.
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.