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http://ipicyt.repositorioinstitucional.mx/jspui/handle/1010/2369| Voltage-Dependent Protonation of the Calcium Pocket Enable Activation of the Calcium-Activated Chloride Channel Anoctamin-1 (TMEM16A) | |
| Ma Guadalupe Segura Covarrubias IVAN ARAEL ARECHIGA FIGUEROA JOSE JUAN DE JESUS PEREZ ALFREDO SANCHEZ SOLANO GLORIA PATRICIA PEREZ CORNEJO Jorge Arreola | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| https://doi.org/10.1038/s41598-020-62860-9 | |
| Ca2+-activated Cl- channel Inhibition Currents Contributes Expression Mechanism Cells | |
| "Anoctamin-1 (ANO1 or TMEM16A) is a homo-dimeric Ca2+-activated Cl− channel responsible for essential physiological processes. Each monomer harbours a pore and a Ca2+-binding pocket; the voltage-dependent binding of two intracellular Ca2+ ions to the pocket gates the pore. However, in the absence of intracellular Ca2+ voltage activates TMEM16A by an unknown mechanism. Here we show voltage-activated anion currents that are outwardly rectifying, time-independent with fast or absent tail currents that are inhibited by tannic and anthracene-9-carboxylic acids. Since intracellular protons compete with Ca2+ for binding sites in the pocket, we hypothesized that voltage-dependent titration of these sites would induce gating. Indeed intracellular acidification enabled activation of TMEM16A by voltage-dependent protonation, which enhanced the open probability of the channel. Mutating Glu/Asp residues in the Ca2+-binding pocket to glutamine (to resemble a permanent protonated Glu) yielded channels that were easier to activate at physiological pH. Notably, the response of these mutants to intracellular acidification was diminished and became voltage-independent. Thus, voltage-dependent protonation of glutamate/aspartate residues (Glu/Asp) located in the Ca2+-binding pocket underlines TMEM16A activation in the absence of intracellular Ca2+." | |
| Nature Publishing Group | |
| 2020 | |
| Artículo | |
| Segura-Covarrubias, G., Aréchiga-Figueroa, I.A., De Jesús-Pérez, J.J. et al. Voltage-Dependent Protonation of the Calcium Pocket Enable Activation of the Calcium-Activated Chloride Channel Anoctamin-1 (TMEM16A). Sci Rep 10, 6644 (2020). https://doi.org/10.1038/s41598-020-62860-9 | |
| CIENCIAS TECNOLÓGICAS | |
| Versión publicada | |
| publishedVersion - Versión publicada | |
| Aparece en las colecciones: | Publicaciones Científicas Biología Molecular |
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| ScientificReports10(2020)6644.pdf | 3.29 MB | Adobe PDF | Visualizar/Abrir |