| First Author | Ávalos Prado P | Year | 2021 |
| Journal | Cell | Volume | 184 |
| Issue | 2 | Pages | 534-544.e11 |
| PubMed ID | 33373586 | Mgi Jnum | J:301484 |
| Mgi Id | MGI:6505652 | Doi | 10.1016/j.cell.2020.11.047 |
| Citation | Avalos Prado P, et al. (2021) KCNE1 is an auxiliary subunit of two distinct ion channel superfamilies. Cell 184(2):534-544.e11 |
| abstractText | Determination of what is the specificity of subunits composing a protein complex is essential when studying gene variants on human pathophysiology. The pore-forming alpha-subunit KCNQ1, which belongs to the voltage-gated ion channel superfamily, associates to its beta-auxiliary subunit KCNE1 to generate the slow cardiac potassium IKs current, whose dysfunction leads to cardiac arrhythmia. Using pharmacology, gene invalidation, and single-molecule fluorescence assays, we found that KCNE1 fulfils all criteria of a bona fide auxiliary subunit of the TMEM16A chloride channel, which belongs to the anoctamin superfamily. Strikingly, assembly with KCNE1 switches TMEM16A from a calcium-dependent to a voltage-dependent ion channel. Importantly, clinically relevant inherited mutations within the TMEM16A-regulating domain of KCNE1 abolish the TMEM16A modulation, suggesting that the TMEM16A-KCNE1 current may contribute to inherited pathologies. Altogether, these findings challenge the dogma of the specificity of auxiliary subunits regarding protein complexes and questions ion channel classification. |
