ArticleThe Journal of general physiology2014
Activation of the Ano1 (TMEM16A) chloride channel by calcium is not mediated by calmodulin.
Article in The Journal of general physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 70 citations in OpenAlex.
- Review
- Niclosamide potentiates TMEM16A and induces vasoconstriction.The Journal of general physiology · 2024Article
- Function and Regulation of the Calcium-Activated Chloride Channel Anoctamin 1 (TMEM16A).Handbook of experimental pharmacology · 2024Article
- Phosphatidylinositol 4,5-Bisphosphate and Cholesterol Regulators of the Calcium-Activated Chloride Channels TMEM16A and TMEM16B.Advances in experimental medicine and biology · 2023Article
- CaCell calcium · 2022Article
- 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
- Calmodulin-Dependent Regulation of Overexpressed but Not Endogenous TMEM16A Expressed in Airway Epithelial Cells.Membranes · 2021Article
- Specific PIPCommunications biology · 2021Article
- Advances in CaExperimental and therapeutic medicine · 2020Review
- A network of phosphatidylinositol 4,5-bisphosphate binding sites regulates gating of the CaProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Molecular basis of PIPNature communications · 2019Article
- Comparison of ion transport determinants between a TMEM16 chloride channel and phospholipid scramblase.The Journal of general physiology · 2019Article
- An allosteric mechanism of inactivation in the calcium-dependent chloride channel BEST1.The Journal of general physiology · 2018Article
- Known structures and unknown mechanisms of TMEM16 scramblases and channels.The Journal of general physiology · 2018Review
- Calcium-Activated ClInternational journal of molecular sciences · 2018Review
- Phosphatidylinositol 4,5-bisphosphate, cholesterol, and fatty acids modulate the calcium-activated chloride channel TMEM16A (ANO1).Biochimica et biophysica acta. Molecular and cell biology of lipids · 2018Article
- Bioinformatic characterization of the Anoctamin Superfamily of Ca2+-activated ion channels and lipid scramblases.PloS one · 2018Article
- Epithelial transport inThe Journal of general physiology · 2017Review
- Lipids and ions traverse the membrane by the same physical pathway in the nhTMEM16 scramblase.eLife · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The Ca(2+)-activated Cl channel anoctamin-1 (Ano1; Tmem16A) plays a variety of physiological roles, including epithelial fluid secretion. Ano1 is activated by increases in intracellular Ca(2+), but there is uncertainty whether Ca(2+) binds directly to Ano1 or whether phosphorylation or additional Ca(2+)-binding subunits like calmodulin (CaM) are required. Here we show that CaM is not necessary for activation of Ano1 by Ca(2+) for the following reasons. (a) Exogenous CaM has no effect on Ano1 currents in inside-out excised patches. (b) Overexpression of Ca(2+)-insensitive mutants of CaM have no effect on Ano1 currents, whereas they eliminate the current mediated by the small-conductance Ca(2+)-activated K(+) (SK2) channel. (c) Ano1 does not coimmunoprecipitate with CaM, whereas SK2 does. Furthermore, Ano1 binds very weakly to CaM in pull-down assays. (d) Ano1 is activated in excised patches by low concentrations of Ba(2+), which does not activate CaM. In addition, we conclude that reversible phosphorylation/dephosphorylation is not required for current activation by Ca(2+) because the current can be repeatedly activated in excised patches in the absence of ATP or other high-energy compounds. Although Ano1 is blocked by the CaM inhibitor trifluoperazine (TFP), we propose that TFP inhibits the channel in a CaM-independent manner because TFP does not inhibit Ano1 when applied to the cytoplasmic side of excised patches. These experiments lead us to conclude that CaM is not required for activation of Ano1 by Ca(2+). Although CaM is not required for channel opening by Ca(2+), work of other investigators suggests that CaM may have effects in modulating the biophysical properties of the channel.
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