ArticleThe Journal of biological chemistry2017
Modulation of TMEM16A channel activity by the von Willebrand factor type A (VWA) domain of the calcium-activated chloride channel regulator 1 (CLCA1).
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Copine-6 is a TRPM3 escort protein controlling the sensitivity of sensory neurons to noxious heat.The EMBO journal · 2025Article
- Structure and Function of Calcium-Activated Chloride Channels and Phospholipid Scramblases in the TMEM16 Family.Handbook of experimental pharmacology · 2024Review
- Intestinal mucus components and secretion mechanisms: what we do and do not know.Experimental & molecular medicine · 2023Review
- Polymodal Control of TMEM16x Channels and Scramblases.International journal of molecular sciences · 2022Review
- Molecular mechanisms of activation and regulation of ANO1-Encoded CaChannels (Austin, Tex.) · 2021Review
- Chloride channel accessory 1 integrates chloride channel activity and mTORC1 in aging-related kidney injury.Aging cell · 2021Article
- CLCA1 Regulates Airway Mucus Production and Ion Secretion Through TMEM16A.International journal of molecular sciences · 2021Article
- How Dysregulated Ion Channels and Transporters Take a Hand in Esophageal, Liver, and Colorectal Cancer.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Analysis of Lung Gene Expression Reveals a Role for ClAmerican journal of respiratory cell and molecular biology · 2020Article
- Pharmacological Inhibition and Activation of the CaInternational journal of molecular sciences · 2020Article
- TMEM16A: An Alternative Approach to Restoring Airway Anion Secretion in Cystic Fibrosis?International journal of molecular sciences · 2020Review
- Structural and Biophysical Analysis of the CLCA1 VWA Domain Suggests Mode of TMEM16A Engagement.Cell reports · 2020Article
- Calcium-Activated Chloride Channel ANO1/TMEM16A: Regulation of Expression and Signaling.Frontiers in physiology · 2020Review
- Interplay Between Ion Channels and the Wnt/β-Catenin Signaling Pathway in Cancers.Frontiers in pharmacology · 2020Review
- Calcium-activated chloride channel regulator 1 (CLCA1) forms non-covalent oligomers in colonic mucus and has mucin 2-processing properties.The Journal of biological chemistry · 2019Article
- Calcium-activated chloride channel regulator 1 (CLCA1): More than a regulator of chloride transport and mucus production.The World Allergy Organization journal · 2019Article
- Emerging roles for multifunctional ion channel auxiliary subunits in cancer.Cell calcium · 2019Review
- Calcium-activated chloride channel regulator 1 as a prognostic biomarker in pancreatic ductal adenocarcinoma.BMC cancer · 2018Article
- Calcium-activated Chloride Channel Regulator 1 (CLCA1) Controls Mucus Expansion in Colon by Proteolytic Activity.EBioMedicine · 2018Article
- A three-way inter-molecular network accounts for the CaThe Journal of biological chemistry · 2018Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Calcium-activated chloride channels (CaCCs) are key players in transepithelial ion transport and fluid secretion, smooth muscle constriction, neuronal excitability, and cell proliferation. The CaCC regulator 1 (CLCA1) modulates the activity of the CaCC TMEM16A/Anoctamin 1 (ANO1) by directly engaging the channel at the cell surface, but the exact mechanism is unknown. Here we demonstrate that the von Willebrand factor type A (VWA) domain within the cleaved CLCA1 N-terminal fragment is necessary and sufficient for this interaction. TMEM16A protein levels on the cell surface were increased in HEK293T cells transfected with CLCA1 constructs containing the VWA domain, and TMEM16A-like currents were activated. Similar currents were evoked in cells exposed to secreted VWA domain alone, and these currents were significantly knocked down by TMEM16A siRNA. VWA-dependent TMEM16A modulation was not modified by the S357N mutation, a VWA domain polymorphism associated with more severe meconium ileus in cystic fibrosis patients. VWA-activated currents were significantly reduced in the absence of extracellular Mg
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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.