ArticlePloS one2013
Endocytosis of HERG is clathrin-independent and involves arf6.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Development of an Absolute Quantification Method for hERG Using PRM with Single Isotopologue in-Sample Calibration.ACS omega · 2024Article
- Arf6 is required for endocytosis and filamentous actin assembly during angiogenesis in vitro.Microcirculation (New York, N.Y. : 1994) · 2023Article
- The cellular pathways that maintain the quality control and transport of diverse potassium channels.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
- The dual-function chemokine receptor CCR2 drives migration and chemokine scavenging through distinct mechanisms.Science signaling · 2023Article
- Internalization of Polymeric Bacterial Peptidoglycan Occurs through Either Actin or Dynamin Dependent Pathways.Microorganisms · 2022Article
- Influencing factors for the decline of limb muscle strength and the association with all-cause mortality: evidence from a nationwide population-based cohort study.Aging clinical and experimental research · 2022Article
- Identification of miR-145 as a regulator of the cardiomyocyte inflammatory response and oxidative stress under hyperglycemia.Experimental and therapeutic medicine · 2021Article
- Review
- Fluvastatin inhibits Rab5-mediated IKs internalization caused by chronic CaJournal of molecular and cellular cardiology · 2019Article
- Development of a High-Throughput Flow Cytometry Assay to Monitor Defective Trafficking and Rescue of Long QT2 Mutant hERG Channels.Frontiers in physiology · 2018Article
- hERG quality control and the long QT syndrome.The Journal of physiology · 2016Review
- Translational toxicology and rescue strategies of the hERG channel dysfunction: biochemical and molecular mechanistic aspects.Acta pharmacologica Sinica · 2014Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The hERG potassium channel is critical for repolarisation of the cardiac action potential. Reduced expression of hERG at the plasma membrane, whether caused by hereditary mutations or drugs, results in long QT syndrome and increases the risk of ventricular arrhythmias. Thus, it is of fundamental importance to understand how the density of this channel at the plasma membrane is regulated. We used antibodies to an extracellular native or engineered epitope, in conjunction with immunofluorescence and ELISA, to investigate the mechanism of hERG endocytosis in recombinant cells and validated the findings in rat neonatal cardiac myocytes. The data reveal that this channel undergoes rapid internalisation, which is inhibited by neither dynasore, an inhibitor of dynamin, nor a dominant negative construct of Rab5a, into endosomes that are largely devoid of the transferrin receptor. These results support a clathrin-independent mechanism of endocytosis and exclude involvement of dynamin-dependent caveolin and RhoA mechanisms. In agreement, internalised hERG displayed marked overlap with glycosylphosphatidylinositol-anchored GFP, a clathrin-independent cargo. Endocytosis was significantly affected by cholesterol extraction with methyl-β-cyclodextrin and inhibition of Arf6 function with dominant negative Arf6-T27N-eGFP. Taken together, we conclude that hERG undergoes clathrin-independent endocytosis via a mechanism involving Arf6.
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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.