2023
Pharmacological Modulation of Energy and Metabolic Pathways Protects Hearing in the Fus1/Tusc2 Knockout Model of Mitochondrial Dysfunction and Oxidative Stress
Tan W, Santos-Sacchi J, Tonello J, Shanker A, Ivanova A. Pharmacological Modulation of Energy and Metabolic Pathways Protects Hearing in the Fus1/Tusc2 Knockout Model of Mitochondrial Dysfunction and Oxidative Stress. Antioxidants 2023, 12: 1225. PMID: 37371955, PMCID: PMC10294946, DOI: 10.3390/antiox12061225.Peer-Reviewed Original ResearchPharmacological modulationKO miceMitochondrial metabolismComparative gene expression analysisMetabolic pathwaysOxidative stressCritical biological processesHearing-related genesDrug-specific responsesPremature hearing lossGene expression analysisAdrenal axisHearing lossImmune responseMitochondrial morphologyMotor proteinsExpression analysisVoltage-gated channelsBiological processesMTOR pathwayNormal hearingPronounced upregulationMolecular pathwaysMitochondrial activityEnergy sensingMegahertz Sampling of Prestin (SLC26a5) Voltage-Sensor Charge Movements in Outer Hair Cell Membranes Reveals Ultrasonic Activity that May Support Electromotility and Cochlear Amplification
Santos-Sacchi J, Bai J, Navaratnam D. Megahertz Sampling of Prestin (SLC26a5) Voltage-Sensor Charge Movements in Outer Hair Cell Membranes Reveals Ultrasonic Activity that May Support Electromotility and Cochlear Amplification. Journal Of Neuroscience 2023, 43: 2460-2468. PMID: 36868859, PMCID: PMC10082455, DOI: 10.1523/jneurosci.2033-22.2023.Peer-Reviewed Original ResearchConceptsConformational switchingMammalian hearingMembrane motor proteinCochlear amplificationMotor protein prestinVoltage-sensor charge movementOuter hair cell electromotilityHair cell electromotilityProtein prestinMotor proteinsConformation switchingCharge movementPrestinPrestin activityCell membraneOHC electromotilityHair cell membraneElectromotilityTransmembrane voltageOrgan of CortiAmplificationMammalsMembrane capacitanceProtein
2020
Maturation of Voltage-induced Shifts in SLC26a5 (Prestin) Operating Point during Trafficking and Membrane Insertion
Zhai F, Song L, Bai JP, Dai C, Navaratnam D, Santos-Sacchi J. Maturation of Voltage-induced Shifts in SLC26a5 (Prestin) Operating Point during Trafficking and Membrane Insertion. Neuroscience 2020, 431: 128-133. PMID: 32061780, PMCID: PMC8720582, DOI: 10.1016/j.neuroscience.2020.02.003.Peer-Reviewed Original ResearchConceptsMembrane motor proteinVoltage-dependent proteinsMembrane insertionOuter hair cellsMotor proteinsPrestin densityHEK cell linesConformational changesBiophysical forcesOHC electromotilityProteinCell linesMembrane potentialCooperative interactionsPrestinHair cellsCochlear amplificationTransmembrane voltageNonlinear capacitanceMammalsTraffickingVoltage-induced shiftElectromotilityMaturationMembrane
2013
Real Time Measures of Prestin Charge and Fluorescence during Plasma Membrane Trafficking Reveal Sub-Tetrameric Activity
Bian S, Navaratnam D, Santos-Sacchi J. Real Time Measures of Prestin Charge and Fluorescence during Plasma Membrane Trafficking Reveal Sub-Tetrameric Activity. PLOS ONE 2013, 8: e66078. PMID: 23762468, PMCID: PMC3677934, DOI: 10.1371/journal.pone.0066078.Peer-Reviewed Original ResearchConceptsObligate tetramerPlasma membraneMembrane motor proteinIntegral membrane proteinsTetracycline-inducible cell lineMembrane proteinsMotor proteinsPrestin densityTemperature blockPrestinFluorescence measuresMembrane fluorescenceCell linesNonlinear capacitanceCochlear amplificationProteinTetramerMembraneFluorescencePrevious observationsVoltage clampFluorescence methodCellsAmplification
2005
On the Effect of Prestin on the Electrical Breakdown of Cell Membranes
Navarrete EG, Santos-Sacchi J. On the Effect of Prestin on the Electrical Breakdown of Cell Membranes. Biophysical Journal 2005, 90: 967-974. PMID: 16299081, PMCID: PMC1367121, DOI: 10.1529/biophysj.105.064105.Peer-Reviewed Original ResearchConceptsTSA cellsWhole cell levelVoltage-dependent activityGuinea pig OHCsOuter hair cell motor proteinMotor proteinsPM domainsMaximum transmembrane potentialPrestin activityMembrane susceptibilityTransmembrane potentialCell membranePrestinTsA201 cellsBiophysical influencesMembrane stiffnessElectroporationCellsBasal portionSignificant resistanceMembrane capacitanceProteinElectromotilityAuditory sensitivitySusceptibilityN-Terminal-Mediated Homomultimerization of Prestin, the Outer Hair Cell Motor Protein
Navaratnam D, Bai JP, Samaranayake H, Santos-Sacchi J. N-Terminal-Mediated Homomultimerization of Prestin, the Outer Hair Cell Motor Protein. Biophysical Journal 2005, 89: 3345-3352. PMID: 16113116, PMCID: PMC1366831, DOI: 10.1529/biophysj.105.068759.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric SiteAmino Acid SequenceAnimalsCell MembraneCell SeparationCHO CellsCricetinaeDimerizationElectric CapacitanceElectric ConductivityElectrophysiologyFlow CytometryFluorescence Resonance Energy TransferGerbillinaeGreen Fluorescent ProteinsHair Cells, Auditory, OuterMechanotransduction, CellularMembrane PotentialsMicroscopy, ConfocalMicroscopy, FluorescenceModels, BiologicalMolecular Motor ProteinsMolecular Sequence DataMutationProtein BindingProtein ConformationProtein Structure, TertiaryProteinsTransfectionConceptsOuter Hair Cell Motor ProteinStructure-function relationsNormal membrane targetingMammalian cochlear amplificationIntact N-terminusMembrane targetingDomain proteinsMembrane topologyFluorescence resonance energy transferCell mechanical responsePrestin moleculesMembrane motorMotor proteinsN-terminusShort truncationsPrestinResonance energy transferIntracellular terminiAllosteric modulationProteinTerminusCochlear amplificationVoltage sensingHomomultimerizationModified activity
2004
Protein- and Lipid-Reactive Agents Alter Outer Hair Cell Lateral Membrane Motor Charge Movement
Santos-Sacchi J, Wu M. Protein- and Lipid-Reactive Agents Alter Outer Hair Cell Lateral Membrane Motor Charge Movement. The Journal Of Membrane Biology 2004, 200: 83-92. PMID: 15520906, DOI: 10.1007/s00232-004-0699-2.Peer-Reviewed Original Research
2003
Cl− flux through a non‐selective, stretch‐sensitive conductance influences the outer hair cell motor of the guinea‐pig
Rybalchenko V, Santos‐Sacchi J. Cl− flux through a non‐selective, stretch‐sensitive conductance influences the outer hair cell motor of the guinea‐pig. The Journal Of Physiology 2003, 547: 873-891. PMID: 12562920, PMCID: PMC2342734, DOI: 10.1111/j.1469-7793.2003.00873.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarbenoxoloneCell MembraneChloride ChannelsChloridesCyclooxygenase InhibitorsElectric CapacitanceElectric ConductivityGadoliniumGuinea PigsHair Cells, Auditory, OuterIon Channel GatingMechanotransduction, CellularMembrane PotentialsMercuric ChlorideMicrodialysisNiflumic AcidOctanolsProteinsSulfonic AcidsConceptsOuter hair cell motorLateral membranesVoltage-dependent conformational changesLateral plasma membranePlasma membraneMotor proteinsCell motorProtein transitionsConformational changesRecent identificationPrestinSomatic motilityAllosteric modulationCL sensitivityAnion fluxHair cellsCochlear amplificationAcoustic ratesOuter hair cellsAlternative mechanismComplicated roleMembranePronounced shiftCellsAmplification
2002
Functional motor microdomains of the outer hair cell lateral membrane
Santos-Sacchi J. Functional motor microdomains of the outer hair cell lateral membrane. Pflügers Archiv - European Journal Of Physiology 2002, 445: 331-336. PMID: 12466934, DOI: 10.1007/s00424-002-0928-4.Peer-Reviewed Original ResearchConceptsOperating voltage rangeLateral membranesMammalian inner earOuter hair cell lateral membraneOuter hair cellsMotor proteinsFunctional variationMechanical deformationNeuroepithelial cellsVoltage rangeMicrodomainsWhole cellsMidpoint voltageHair cellsMotor chargeCell characteristicsMembraneCellsNonlinear capacitanceInner ear
2001
Effects of membrane potential and tension on prestin, the outer hair cell lateral membrane motor protein
Santos‐Sacchi J, Shen W, Zheng J, Dallos P. Effects of membrane potential and tension on prestin, the outer hair cell lateral membrane motor protein. The Journal Of Physiology 2001, 531: 661-666. PMID: 11251048, PMCID: PMC2278494, DOI: 10.1111/j.1469-7793.2001.0661h.x.Peer-Reviewed Original ResearchConceptsMembrane tensionMembrane motor proteinMembrane-bound proteinsHuman embryonic kidney cellsLateral plasma membraneEmbryonic kidney cellsMolecular basisPlasma membraneProtein prestinMotor proteinsConformational changesHigh-resolution analysisPrestin activityPrestinKidney cellsMembrane potential