2024
Cell Membrane Tension Gradients, Membrane Flows, and Cellular Processes
Yan Q, Gomis Perez C, Karatekin E. Cell Membrane Tension Gradients, Membrane Flows, and Cellular Processes. Physiology 2024, 39: 231-245. PMID: 38501962, PMCID: PMC11368524, DOI: 10.1152/physiol.00007.2024.Peer-Reviewed Original ResearchNav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia
Nascimento de Lima A, Zhang H, Chen L, Effraim P, Gomis-Perez C, Cheng X, Huang J, Waxman S, Dib-Hajj S. Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia. Brain 2024, 147: 3157-3170. PMID: 38447953, DOI: 10.1093/brain/awae071.Peer-Reviewed Original ResearchDorsal root ganglion neuronsDorsal root ganglionVincristine-induced mechanical allodyniaVincristine-induced peripheral neuropathyMechanical allodyniaVincristine treatmentNav1.8 channelsSmall dorsal root ganglion neuronsDevelopment of mechanical allodyniaTTX-R current densityVoltage-gated sodium channel Nav1.6Vincristine-treated animalsCurrent-clamp recordingsSodium channel Nav1.8Voltage-clamp recordingsReducing current thresholdSodium channel Nav1.6Investigate pathophysiological mechanismsTTX-RHyperpolarizing shiftRoot ganglionAllodyniaGanglion neuronsVincristine administrationPeripheral neuropathy
2022
Membrane fission during bacterial spore development requires cellular inflation driven by DNA translocation
Landajuela A, Braun M, Martínez-Calvo A, Rodrigues CDA, Gomis Perez C, Doan T, Rudner DZ, Wingreen NS, Karatekin E. Membrane fission during bacterial spore development requires cellular inflation driven by DNA translocation. Current Biology 2022, 32: 4186-4200.e8. PMID: 36041438, PMCID: PMC9730832, DOI: 10.1016/j.cub.2022.08.014.Peer-Reviewed Original ResearchConceptsMother cell membraneMembrane fissionMother cellsDNA translocationMembrane tensionLarger mother cellMother cell cytoplasmCell membraneHigh membrane tensionSmaller foresporeDNA translocaseEnergy-limited conditionsForespore compartmentAsymmetric divisionEndospore formationMembrane compartmentsMembrane necksSpore developmentCell divisionMolecular basisForesporeMembrane flowBacillus subtilisCell cytoplasmFisBRapid propagation of membrane tension at retinal bipolar neuron presynaptic terminals
Gomis Perez C, Dudzinski NR, Rouches M, Landajuela A, Machta B, Zenisek D, Karatekin E. Rapid propagation of membrane tension at retinal bipolar neuron presynaptic terminals. Science Advances 2022, 8: eabl4411. PMID: 34985955, DOI: 10.1126/sciadv.abl4411.Peer-Reviewed Original ResearchMembrane tensionMembrane flowStimulation of exocytosisSynaptic vesicle turnoverNeuroendocrine adrenal chromaffin cellsCell divisionVesicle turnoverCellular activitiesCell migrationCell typesAdrenal chromaffin cellsChromaffin cellsGlobal decreasePresynaptic terminalsRapid propagationEndocytosisExocytosisNeuronal terminalsPhagocytosisTurnoverGradientCellsDivisionMigration
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
2020
A 49-residue sequence motif in the C terminus of Nav1.9 regulates trafficking of the channel to the plasma membrane
Sizova D, Huang J, Akin E, Estacion M, Gomis-Perez C, Waxman S, Dib-Hajj S. A 49-residue sequence motif in the C terminus of Nav1.9 regulates trafficking of the channel to the plasma membrane. Journal Of Biological Chemistry 2020, 295: 1077-1090. DOI: 10.1016/s0021-9258(17)49917-0.Peer-Reviewed Original ResearchPlasma membraneC-terminusHEK293 cellsHigh-resolution live microscopyC-terminal motifHeterologous expression systemC-terminal chimerasHigh-throughput assaysSequence motifsCytoplasmic faceHeterologous systemsVoltage-gated sodium channel Nav1.9Live microscopyRecombinant expressionExpression systemLong motifsMechanistic basisFunctional expressionFunctional studiesTerminusLow functional expressionMotifChannel chimeraExpression levelsChimeras
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 channelsCellsResilience to Pain: A Peripheral Component Identified Using Induced Pluripotent Stem Cells and Dynamic Clamp
Mis MA, Yang Y, Tanaka BS, Gomis-Perez C, Liu S, Dib-Hajj F, Adi T, Garcia-Milian R, Schulman BR, Dib-Hajj SD, Waxman SG. Resilience to Pain: A Peripheral Component Identified Using Induced Pluripotent Stem Cells and Dynamic Clamp. Journal Of Neuroscience 2018, 39: 382-392. PMID: 30459225, PMCID: PMC6335750, DOI: 10.1523/jneurosci.2433-18.2018.Peer-Reviewed Original ResearchMeSH KeywordsAdultChildChronic PainErythromelalgiaExcitatory Postsynaptic PotentialsExomeFemaleGanglia, SpinalHumansImmunohistochemistryIndividualityInduced Pluripotent Stem CellsKCNQ Potassium ChannelsMaleMembrane PotentialsNAV1.7 Voltage-Gated Sodium ChannelPain MeasurementPatch-Clamp TechniquesResilience, PsychologicalSensory Receptor CellsConceptsWhole-exome sequencingPeripheral sensory neuronsSensory neuronsSpecific gene variantsGene variantsPluripotent stem cell-derived sensory neuronsInterindividual differencesDorsal root ganglion neuronsExome sequencingDifferent pain profilesDRG neuron excitabilityDynamic clampPeripheral nervous systemStem cellsPain ProfilePluripotent stem cellsChronic painPeripheral mechanismsGanglion neuronsNeuron excitabilityPainNervous systemHuman genetic modelsNeuronsDifferent gene variantsStructural 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 statesLack of correlation between surface expression and currents in epileptogenic AB-calmodulin binding domain Kv7.2 potassium channel mutants
Alaimo A, Etxeberria A, Gómez-Posada JC, Gomis-Perez C, Fernández-Orth J, Malo C, Villarroel A. Lack of correlation between surface expression and currents in epileptogenic AB-calmodulin binding domain Kv7.2 potassium channel mutants. Channels 2018, 12: 299-310. PMID: 30126342, PMCID: PMC6161613, DOI: 10.1080/19336950.2018.1511512.Peer-Reviewed Original Research
2017
Calmodulin confers calcium sensitivity to the stability of the distal intracellular assembly domain of Kv7.2 channels
Alaimo A, Nuñez E, Aivar P, Fernández-Orth J, Gomis-Perez C, Bernardo-Seisdedos G, Malo C, Villarroel A. Calmodulin confers calcium sensitivity to the stability of the distal intracellular assembly domain of Kv7.2 channels. Scientific Reports 2017, 7: 13425. PMID: 29044210, PMCID: PMC5647379, DOI: 10.1038/s41598-017-13811-4.Peer-Reviewed Original ResearchDifferential 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
2016
Ubiquitin-specific Protease 36 (USP36) Controls Neuronal Precursor Cell-expressed Developmentally Down-regulated 4-2 (Nedd4-2) Actions over the Neurotrophin Receptor TrkA and Potassium Voltage-gated Channels 7.2/3 (Kv7.2/3)*
Anta B, Martín-Rodríguez C, Gomis-Perez C, Calvo L, López-Benito S, Calderón-García AA, Vicente-García C, Villarroel Á, Arévalo JC. Ubiquitin-specific Protease 36 (USP36) Controls Neuronal Precursor Cell-expressed Developmentally Down-regulated 4-2 (Nedd4-2) Actions over the Neurotrophin Receptor TrkA and Potassium Voltage-gated Channels 7.2/3 (Kv7.2/3)*. Journal Of Biological Chemistry 2016, 291: 19132-19145. PMID: 27445338, PMCID: PMC5009282, DOI: 10.1074/jbc.m116.722637.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationEndosomal Sorting Complexes Required for TransportGene Expression RegulationHEK293 CellsHumansKCNQ2 Potassium ChannelKCNQ3 Potassium ChannelMiceNedd4 Ubiquitin Protein LigasesNeural Stem CellsPC12 CellsProtein BindingRatsReceptor, trkAUbiquitin ThiolesteraseUbiquitin-Protein LigasesConceptsNedd4-2Association of TrkAE3 ubiquitin ligasesTrkA ubiquitinationPC12 cell differentiationTrkA neurotrophin receptorTrkA activationNeuronal precursor cellsUbiquitin ligasesExpression disruptsChannel regulationUbiquitinationUSP36Cell differentiationImportant regulatorPrecursor cellsComplex formationActivation kineticsNeurotrophin receptors TrkAReceptor TrkATrkARegulationExpressionLigasesNeurotrophin receptorStructural Insights of the Calcium Mediated Reorganization of the Calmodulin/Kv7.2 Channel Complex
Villarroel A, Bernardo-Seisdedos G, Alaimo A, Gomis-Perez C, Alberdi A, Malo C, Areso P, Millet O. Structural Insights of the Calcium Mediated Reorganization of the Calmodulin/Kv7.2 Channel Complex. Biophysical Journal 2016, 110: 102a. DOI: 10.1016/j.bpj.2015.11.608.Peer-Reviewed Original ResearchTRPA1 Is Expressed in Central But Not in Peripheral Glia
Vellani, V. , Gomis-Perez C. , Pinti, M. , Prandini, M. , Pavesi, G. , Giacomoni, C. and Caprini, M. (2016) TRPA1 Is Expressed in Central But Not in Peripheral Glia. Journal of Biomedical Science and Engineering, 9, 515-531. doi: 10.4236/jbise.2016.911046.Peer-Reviewed Original Research
2015
Uncoupling PIP2-calmodulin regulation of Kv7.2 channels by an assembly destabilizing epileptogenic mutation
Alberdi A, Gomis-Perez C, Bernardo-Seisdedos G, Alaimo A, Malo C, Aldaregia J, Lopez-Robles C, Areso P, Butz E, Wahl-Schott C, Villarroel A. Uncoupling PIP2-calmodulin regulation of Kv7.2 channels by an assembly destabilizing epileptogenic mutation. Journal Of Cell Science 2015, 128: 4014-4023. PMID: 26359296, DOI: 10.1242/jcs.176420.Peer-Reviewed Original ResearchEpilepsy-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 fragmentDisruption of Assembly/Calmodulin-Binding Coupling and Calmodulin-Dependent Potentiation of Kv7.2 Channels by a Epileptogenic Helix D Mutation
Alberdi A, Bernardo-Seisdedos G, Gomis-Perez C, Alaimo A, Malo C, Butz E, Wahl-Schott C, Areso P, Villarroel A. Disruption of Assembly/Calmodulin-Binding Coupling and Calmodulin-Dependent Potentiation of Kv7.2 Channels by a Epileptogenic Helix D Mutation. Biophysical Journal 2015, 108: 349a. DOI: 10.1016/j.bpj.2014.11.1912.Peer-Reviewed Original ResearchPIP2 and Surface Expression Underlie Apo-Calmodulin Dependent Kv7.2/KCNQ2 Current Potentiation
Gomis-Perez C, Soldovieri M, Alberdi A, Ambrosino P, Di Maria M, Alaimo A, Bernardo-Seisdedos G, Malo C, Areso P, Taglialatela M, Villarroel A. PIP2 and Surface Expression Underlie Apo-Calmodulin Dependent Kv7.2/KCNQ2 Current Potentiation. Biophysical Journal 2015, 108: 349a. DOI: 10.1016/j.bpj.2014.11.1910.Peer-Reviewed Original ResearchCalmodulin Binding to a Novel Site in the AB Module of Kv7.2 Subunits Regulates Surface Expression
Bernardo-Seisdedos G, Fernandez-Orth J, Gomis-Perez C, Alaimo A, Alberdi A, Malo C, Areso P, Villarroel A. Calmodulin Binding to a Novel Site in the AB Module of Kv7.2 Subunits Regulates Surface Expression. Biophysical Journal 2015, 108: 24a. DOI: 10.1016/j.bpj.2014.11.153.Peer-Reviewed Original Research