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 channelsCells
2015
An unconventional calmodulin-anchoring site within the AB module of Kv7.2 channels
Gomis-Perez C, Alaimo A, Fernandez-Orth J, Alberdi A, Aivar-Mateo P, Bernardo-Seisdedos G, Malo C, Areso P, Felipe A, Villarroel A. An unconventional calmodulin-anchoring site within the AB module of Kv7.2 channels. Journal Of Cell Science 2015, 128: 3155-3163. PMID: 26148514, DOI: 10.1242/jcs.174128.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsAmino Acid SequenceAnimalsHEK293 CellsHumansKCNQ2 Potassium ChannelMicroscopy, ConfocalMolecular Sequence DataPatch-Clamp TechniquesXenopusConceptsB 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