ArticleThe Journal of biological chemistry2015
Variomics screen identifies the re-entrant loop of the calcium-activated chloride channel ANO1 that facilitates channel activation.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Structure and Function of Calcium-Activated Chloride Channels and Phospholipid Scramblases in the TMEM16 Family.Handbook of experimental pharmacology · 2024Review
- TMEM16A as a potential treatment target for head and neck cancer.Journal of experimental & clinical cancer research : CR · 2022Review
- Phospholipid scrambling by a TMEM16 homolog of Arabidopsis thaliana.The FEBS journal · 2022Article
- Lysosomal inhibition sensitizes TMEM16A-expressing cancer cells to chemotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Discovery of 4-arylthiophene-3-carboxylic acid as inhibitor of ANO1 and its effect as analgesic agent.Acta pharmaceutica Sinica. B · 2021Article
- Identification and characterization of hippuristanol-resistant mutants reveals eIF4A1 dependencies within mRNA 5' leader regions.Nucleic acids research · 2020Article
- TMEM16A Potentiation: A Novel Therapeutic Approach for the Treatment of Cystic Fibrosis.American journal of respiratory and critical care medicine · 2020Article
- CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing's sarcoma.Nature chemical biology · 2020Article
- Discovery of a ZIP7 inhibitor from a Notch pathway screen.Nature chemical biology · 2019Article
- TMEM16A/ANO1 suppression improves response to antibody-mediated targeted therapy of EGFR and HER2/ERBB2.Genes, chromosomes & cancer · 2017Article
- Influence of intracellular Ca2+ and alternative splicing on the pharmacological profile of ANO1 channels.American journal of physiology. Cell physiology · 2016Article
- High Throughput Random Mutagenesis and Single Molecule Real Time Sequencing of the Muscle Nicotinic Acetylcholine Receptor.PloS one · 2016Article
- Gating modes of calcium-activated chloride channels TMEM16A and TMEM16B.The Journal of physiology · 2015Article
- Article
- ANO1/TMEM16A interacts with EGFR and correlates with sensitivity to EGFR-targeting therapy in head and neck cancer.Oncotarget · 2015Article
- Four basic residues critical for the ion selectivity and pore blocker sensitivity of TMEM16A calcium-activated chloride channels.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Anoctamin Calcium-Activated Chloride Channels May Modulate Inhibitory Transmission in the Cerebellar Cortex.PloS one · 2015Article
- Role of volume-regulated and calcium-activated anion channels in cell volume homeostasis, cancer and drug resistance.Channels (Austin, Tex.) · 2015Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The calcium-activated chloride channel ANO1 regulates multiple physiological processes. However, little is known about the mechanism of channel gating and regulation of ANO1 activity. Using a high-throughput, random mutagenesis-based variomics screen, we generated and functionally characterized ∼6000 ANO1 mutants and identified novel mutations that affected channel activity, intracellular trafficking, or localization of ANO1. Mutations such as S741T increased ANO1 calcium sensitivity and rendered ANO1 calcium gating voltage-independent, demonstrating a critical role of the re-entrant loop in coupling calcium and voltage sensitivity of ANO1 and hence in regulating ANO1 activation. Our data present the first unbiased and comprehensive study of the structure-function relationship of ANO1. The novel ANO1 mutants reported have diverse functional characteristics, providing new tools to study ANO1 function in biological systems, paving the path for a better understanding of the function of ANO1 and its role in health and diseases.
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