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
2015
Epilepsy-causing mutations in Kv7.2 C-terminus affect binding and functional modulation by calmodulin
Ambrosino P, Alaimo A, Bartollino S, Manocchio L, De Maria M, Mosca I, Gomis-Perez C, Alberdi A, Scambia G, Lesca G, Villarroel A, Taglialatela M, Soldovieri MV. Epilepsy-causing mutations in Kv7.2 C-terminus affect binding and functional modulation by calmodulin. Biochimica Et Biophysica Acta 2015, 1852: 1856-1866. PMID: 26073431, DOI: 10.1016/j.bbadis.2015.06.012.Peer-Reviewed Original ResearchBenign familial neonatal seizuresKv7.2/Kv7.3 channelsFunctional modulationPatch-clamp recordingsPotential therapeutic approachFamilial neonatal seizuresComplete functional lossNeonatal seizuresEpileptic encephalopathyPathogenetic mechanismsTherapeutic approachesChannel dysfunctionCaM affinityEpilepsy-causing mutationsKv7.3 channelsFunctional lossCaM overexpressionFunctional changesEpileptic diseasePhenotypic presentationChannel subunitsKCNQ2 geneKv7.2Significant alterationsC-terminal fragment
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
2012
Surface Expression and Subunit Specific Control of Steady Protein Levels by the Kv7.2 Helix A-B Linker
Aivar P, Fernández-Orth J, Gomis-Perez C, Alberdi A, Alaimo A, Rodríguez MS, Giraldez T, Miranda P, Areso P, Villarroel A. Surface Expression and Subunit Specific Control of Steady Protein Levels by the Kv7.2 Helix A-B Linker. PLOS ONE 2012, 7: e47263. PMID: 23115641, PMCID: PMC3480381, DOI: 10.1371/journal.pone.0047263.Peer-Reviewed Original ResearchConceptsB linkerPlasma membraneHelix ATetrameric channel assemblyIntracellular C-terminusAmino acid sequenceSteady-state amountsSurface expressionSteady-state levelsProtein degradationAcid sequenceC-terminusChannel assemblyFunctional channelsIntracellular distributionProtein levelsProteinSpecific controlKv7.2Detectable impactM-currentExpressionNeuronal excitabilityMembraneIntrinsic signals