ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2016
PKCα regulates TMEM16A-mediated Cl⁻ secretion in human biliary cells.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Cholangiocyte biology in primary sclerosing cholangitis and other cholangiopathies: pathogenesis, clinical insights, and experimental tools.Physiological reviews · 2026Review
- Mechanism of action and therapeutic value of anoctamin-1 in gastrointestinal cancers.Frontiers in immunology · 2025Review
- Electromechanical Regulation Underlying Protein Nanoparticle-Induced Osmotic Pressure in Neurotoxic Edema.International journal of nanomedicine · 2025Article
- TMEM16 proteins: CaInternational journal of molecular medicine · 2024Review
- The role of anoctamin 1 in liver disease.Journal of cellular and molecular medicine · 2024Review
- Effects of natural products on functional constipation: analysis of active ingredient and mechanism.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Protein nanoparticles induce the activation of voltage-dependent non-selective ion channels to modulate biological osmotic pressure in cytotoxic cerebral edema.Frontiers in pharmacology · 2024Article
- TMEM16A partners with mTOR to influence pathways of cell survival, proliferation, and migration in cholangiocarcinoma.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Vascular mechanotransduction.Physiological reviews · 2023Review
- Active enterohepatic cycling is not required for the choleretic actions of 24-norUrsodeoxycholic acid in mice.JCI insight · 2023Article
- Identification of the chloride channel, leucine-rich repeat-containing protein 8, subfamily a (LRRC8A), in mouse cholangiocytes.Hepatology (Baltimore, Md.) · 2022Article
- The Prognostic Value and Mechanisms of TMEM16A in Human Cancer.Frontiers in molecular biosciences · 2021Review
- Allosteric modulation of alternatively spliced CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Whole-exome sequencing reveals ANO8 as a genetic risk factor for intrahepatic cholestasis of pregnancy.BMC pregnancy and childbirth · 2020Article
- Dual role of CaCell death & disease · 2020Article
- Signaling through the interleukin-4 and interleukin-13 receptor complexes regulates cholangiocyte TMEM16A expression and biliary secretion.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Mechanosensor transient receptor potential vanilloid member 4 (TRPV4) regulates mouse cholangiocyte secretion and bile formation.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes.Frontiers in cellular neuroscience · 2020Review
- Bile acids stimulate cholangiocyte fluid secretion by activation of transmembrane member 16A ClHepatology (Baltimore, Md.) · 2018Article
- Calcium Signaling in Liver Injury and Regeneration.Frontiers in medicine · 2018Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
TMEM16A is a newly identified Ca(2+)-activated Cl(-) channel in biliary epithelial cells (BECs) that is important in biliary secretion. While extracellular ATP stimulates TMEM16A via binding P2 receptors and increasing intracellular Ca(2+) concentration ([Ca(2+)]i), the regulatory pathways have not been elucidated. Protein kinase C (PKC) contributes to ATP-mediated secretion in BECs, although its potential role in TMEM16A regulation is unknown. To determine whether PKCα regulates the TMEM16A-dependent membrane Cl(-) transport in BECs, studies were performed in human biliary Mz-cha-1 cells. Addition of extracellular ATP induced a rapid translocation of PKCα from the cytosol to the plasma membrane and activation of whole cell Ca(2+)-activated Cl(-) currents. Currents demonstrated outward rectification and reversal at 0 mV (properties consistent with TMEM16A) and were inhibited by either molecular (siRNA) or pharmacologic (PMA or Gö6976) inhibition of PKCα. Intracellular dialysis with recombinant PKCα activated Cl(-) currents with biophysical properties identical to TMEM16A in control cells but not in cells after transfection with TMEM16A siRNA. In conclusion, our studies demonstrate that PKCα is coupled to ATP-stimulated TMEM16A activation in BECs. Targeting this ATP-Ca(2+)-PKCα signaling pathway may represent a therapeutic strategy to increase biliary secretion and promote bile formation.
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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.