2021
An epilepsy-causing mutation leads to co-translational misfolding of the Kv7.2 channel
Urrutia J, Aguado A, Gomis-Perez C, Muguruza-Montero A, Ballesteros OR, Zhang J, Nuñez E, Malo C, Chung HJ, Leonardo A, Bergara A, Villarroel A. An epilepsy-causing mutation leads to co-translational misfolding of the Kv7.2 channel. BMC Biology 2021, 19: 109. PMID: 34020651, PMCID: PMC8138981, DOI: 10.1186/s12915-021-01040-1.Peer-Reviewed Original ResearchConceptsKv7.2 channelsChannel functionSequences of proteinsNon-native configurationsNascent chainsProper foldingEpilepsy-causing mutationsIQ motifResponsive domainHuman diseasesHelix ANative conformationFolding routeIon channelsKCNQ2 geneMutationsNeuronal compartmentsFoldingMisfoldingProteinKey pathogenic mechanismsPathogenic variantsSilico studiesPathogenic mechanismsSide chains
2018
Homomeric Kv7.2 current suppression is a common feature in KCNQ2 epileptic encephalopathy
Gomis‐Pérez C, Urrutia J, Marcé‐Grau A, Malo C, López‐Laso E, Felipe‐Rucián A, Raspall‐Chaure M, Macaya A, Villarroel A. Homomeric Kv7.2 current suppression is a common feature in KCNQ2 epileptic encephalopathy. Epilepsia 2018, 60: 139-148. PMID: 30478917, DOI: 10.1111/epi.14609.Peer-Reviewed Original ResearchConceptsKv7.2 channelsDe novo mutantsWild type Kv7.2Dominant-negative behaviorGenotype-phenotype relationshipsGenetic balanceBisphosphate depletionMutantsHomomeric channelsDNA ratioSubunitsKv7.3 subunitsKv7.2Kv7.3Milder phenotypeMutationsM-currentKCNQ2Common featureNeuronal connectionsRescueKv7.2/Kv7.3 channelsPhenotypeKv7.3 channelsCellsStructural basis and energy landscape for the Ca2+ gating and calmodulation of the Kv7.2 K+ channel
Bernardo-Seisdedos G, Nuñez E, Gomis-Perez C, Malo C, Villarroel Á, Millet O. Structural basis and energy landscape for the Ca2+ gating and calmodulation of the Kv7.2 K+ channel. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 2395-2400. PMID: 29463698, PMCID: PMC5873240, DOI: 10.1073/pnas.1800235115.Peer-Reviewed Original ResearchConceptsC-lobeKey biological signalsPrincipal molecular componentsAssociation of helicesTransmembrane regionStructural basisFunction of CaKv7.2 channelsBasal cytosolic CaConformational rearrangementsN-lobeInactive stateKey controllerMolecular componentsCytosolic CaIntracellular CaKv7.2HelixInactive channelsM-currentBiological signalsCalcification stateMillisecond timeNeuronal excitabilityPopulated excited states
2017
Differential Regulation of PI(4,5)P2 Sensitivity of Kv7.2 and Kv7.3 Channels by Calmodulin
Gomis-Perez C, Soldovieri MV, Malo C, Ambrosino P, Taglialatela M, Areso P, Villarroel A. Differential Regulation of PI(4,5)P2 Sensitivity of Kv7.2 and Kv7.3 Channels by Calmodulin. Frontiers In Molecular Neuroscience 2017, 10: 117. PMID: 28507506, PMCID: PMC5410570, DOI: 10.3389/fnmol.2017.00117.Peer-Reviewed Original ResearchKv7.3 channelsNeuronal excitability controlTonic elevationM-currentKv7.2/3 channelsCurrent inhibitionKv7.2 channelsPathophysiological impactSubunit-specific mannerExcitability controlTransient depletionKinase expressionKv7.2Kv7.3 subunitsPresence of calmodulinCellular availabilitySpecific mannerPotentiationMutant CaMExpression of CaMKv7.3Differential regulationBinding proteinElevationCalcium
2014
Pivoting between Calmodulin Lobes Triggered by Calcium in the Kv7.2/Calmodulin Complex
Alaimo A, Alberdi A, Gomis-Perez C, Fernández-Orth J, Bernardo-Seisdedos G, Malo C, Millet O, Areso P, Villarroel A. Pivoting between Calmodulin Lobes Triggered by Calcium in the Kv7.2/Calmodulin Complex. PLOS ONE 2014, 9: e86711. PMID: 24489773, PMCID: PMC3904923, DOI: 10.1371/journal.pone.0086711.Peer-Reviewed Original ResearchConceptsC-lobeC-terminal segmentPrincipal molecular componentsAssociation of CaMChannel traffickingKv7.2 channelsMolecular mechanismsMolecular eventsEndoplasmic reticulumN-lobeMolecular componentsHelix BCalmodulin complexHelix A.CalmodulinData highlightKv7.2Calmodulin lobesM channelsComplementary approachesNeuronal excitabilityFluorometric assayTraffickingReporterReticulum