2023
The biology of hearing and hearing loss: New insights from naked mole-rats into mechanisms and adaptive responses
Pyott S, Jagersma J, van Tuinen M, Koch U, Lauer A, Park T, Lysakowski A, Santos-Sacchi J, Kumar S, Ryugo D. The biology of hearing and hearing loss: New insights from naked mole-rats into mechanisms and adaptive responses. The Journal Of The Acoustical Society Of America 2023, 154: a298-a299. DOI: 10.1121/10.0023589.Peer-Reviewed Original ResearchBiology of hearingBundle proteinHair bundle proteinAdaptive responseAmino acid substitutionsEusocial lifestyleEvolutionary legacySubterranean speciesPositive selectionComparative organizationAcid substitutionsHair bundlesCochlear amplificationBiologySpeciesProteinNew insightsHearing lossPoor hearingComparative approachDisease modelsMechanistic approachCentral auditory structuresCentral compensationRats resultsMegahertz 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
2022
Physiology and biophysics of outer hair cells: The cells of Dallos
Santos-Sacchi J, Navaratnam D. Physiology and biophysics of outer hair cells: The cells of Dallos. Hearing Research 2022, 423: 108525. PMID: 35599199, DOI: 10.1016/j.heares.2022.108525.Peer-Reviewed Original ResearchConceptsOuter hair cellsHair cellsBasic physiologyCochlear amplificationHearing researchCellsPhysiologySingle particle cryo-EM structure of the outer hair cell motor protein prestin
Butan C, Song Q, Bai JP, Tan WJT, Navaratnam D, Santos-Sacchi J. Single particle cryo-EM structure of the outer hair cell motor protein prestin. Nature Communications 2022, 13: 290. PMID: 35022426, PMCID: PMC8755724, DOI: 10.1038/s41467-021-27915-z.Peer-Reviewed Original ResearchConceptsTransmembrane domainProtein prestinSingle-particle cryo-EM structuresAnti-sigma factor antagonist domainOuter hair cell motor protein prestinCryo-EM structureCryo-electron microscopyMotor protein prestinSLC26 family membersSulfate transportersTransmembrane segmentsPrestin functionÅ resolutionPrestinOHC electromotilityOpen stateCochlear amplificationPutative mechanismsFamily membersDomainRepeatsSLC26A9TransportersMutationsElectromotility
2021
State dependent effects on the frequency response of prestin’s real and imaginary components of nonlinear capacitance
Santos-Sacchi J, Navaratnam D, Tan WJT. State dependent effects on the frequency response of prestin’s real and imaginary components of nonlinear capacitance. Scientific Reports 2021, 11: 16149. PMID: 34373481, PMCID: PMC8352928, DOI: 10.1038/s41598-021-95121-4.Peer-Reviewed Original Research
2020
Functional, Morphological, and Evolutionary Characterization of Hearing in Subterranean, Eusocial African Mole-Rats
Pyott SJ, van Tuinen M, Screven LA, Schrode KM, Bai JP, Barone CM, Price SD, Lysakowski A, Sanderford M, Kumar S, Santos-Sacchi J, Lauer AM, Park TJ. Functional, Morphological, and Evolutionary Characterization of Hearing in Subterranean, Eusocial African Mole-Rats. Current Biology 2020, 30: 4329-4341.e4. PMID: 32888484, PMCID: PMC8109146, DOI: 10.1016/j.cub.2020.08.035.Peer-Reviewed Original ResearchConceptsHair bundle morphologyAmino acid substitutionsAltered hearingLink proteinAcid substitutionsUnique evolutionary trajectoryMolecular evolutionary analysisCochlear amplificationEvolutionary characterizationEvolutionary analysisHuman hearing lossEvolutionary trajectoriesBundle morphologyPrestin functionAfrican Mole-RatsCodon levelSelection pressureSubterranean lifestyleSubterranean rodentsMole-RatUnique lifestyleProteinHair cellsSpeciesOuter hair cellsComplex nonlinear capacitance in outer hair cell macro-patches: effects of membrane tension
Santos-Sacchi J, Tan W. Complex nonlinear capacitance in outer hair cell macro-patches: effects of membrane tension. Scientific Reports 2020, 10: 6222. PMID: 32277153, PMCID: PMC7148382, DOI: 10.1038/s41598-020-63201-6.Peer-Reviewed Original ResearchMaturation 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
2019
Voltage Does Not Drive Prestin (SLC26a5) Electro-Mechanical Activity at High Frequencies Where Cochlear Amplification Is Best
Santos-Sacchi J, Tan W. Voltage Does Not Drive Prestin (SLC26a5) Electro-Mechanical Activity at High Frequencies Where Cochlear Amplification Is Best. IScience 2019, 22: 392-399. PMID: 31812809, PMCID: PMC6911985, DOI: 10.1016/j.isci.2019.11.036.Peer-Reviewed Original ResearchPrestin kinetics and corresponding frequency dependence augment during early development of the outer hair cell within the mouse organ of Corti
Bai JP, Navaratnam D, Santos-Sacchi J. Prestin kinetics and corresponding frequency dependence augment during early development of the outer hair cell within the mouse organ of Corti. Scientific Reports 2019, 9: 16460. PMID: 31712635, PMCID: PMC6848539, DOI: 10.1038/s41598-019-52965-1.Peer-Reviewed Original ResearchConceptsOuter hair cellsPostnatal dayVoltage-sensor charge movementAltricial animalsPostnatal developmentCochlear placeElectrical correlatesHair cellsMouse organsCochlear amplificationEarly developmentAuditory frequencyPrestin activityAuditory capabilitiesCellsCharge movementHigh frequencyResponse increasesPrestin functionMiceActivityMonthsCourse
2018
The Frequency Response of Outer Hair Cell Voltage-Dependent Motility Is Limited by Kinetics of Prestin
Santos-Sacchi J, Tan W. The Frequency Response of Outer Hair Cell Voltage-Dependent Motility Is Limited by Kinetics of Prestin. Journal Of Neuroscience 2018, 38: 5495-5506. PMID: 29899032, PMCID: PMC6001036, DOI: 10.1523/jneurosci.0425-18.2018.Peer-Reviewed Original ResearchConceptsFrequency responseVoltage excitationNonlinear capacitanceFlat frequency responseLow-pass behaviorInterrogation frequencyMechanical responsePiezoelectric couplingCutoff frequencyLow-pass characteristicsLow passElectrical signatureLimiting timeOrders of magnitudeAmplification gainCochlear amplificationKHzΜsMembrane protein prestinVoltageKineticsCapacitanceDamage resultsPhase correspondsElectrical
2015
Tyrosine motifs are required for prestin basolateral membrane targeting
Zhang Y, Moeini-Naghani I, Bai J, Santos-Sacchi J, Navaratnam DS. Tyrosine motifs are required for prestin basolateral membrane targeting. Biology Open 2015, 4: 197-205. PMID: 25596279, PMCID: PMC4365488, DOI: 10.1242/bio.201410629.Peer-Reviewed Original ResearchBasolateral targetingBasolateral surfaceOuter hair cellsBasolateral plasma membraneEpithelial sortingHair cellsYXXΦ motifTyrosine motifEarly endosomesPlasma membranePolarized epitheliumTyrosine residuesPrestinGolgiMDCK cellsTyrosine side chainAP1BPhenotypic measuresBasolateral membraneModel systemEpithelial cellsCochlear amplificationMotifMutationsResidues
2014
Chloride-driven Electromechanical Phase Lags at Acoustic Frequencies Are Generated by SLC26a5, the Outer Hair Cell Motor Protein
Santos-Sacchi J, Song L. Chloride-driven Electromechanical Phase Lags at Acoustic Frequencies Are Generated by SLC26a5, the Outer Hair Cell Motor Protein. Biophysical Journal 2014, 107: 126-133. PMID: 24988347, PMCID: PMC4119270, DOI: 10.1016/j.bpj.2014.05.018.Peer-Reviewed Original Research
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
2011
The still magnificent outer hair cell
Santos-Sacchi J. The still magnificent outer hair cell. Otology Japan 2011, 17: 2-7. DOI: 10.11289/otoljpn1991.17.2.Peer-Reviewed Original Research
2010
Effect of capsaicin on potassium conductance and electromotility of the guinea pig outer hair cell
Wu T, Song L, Shi X, Jiang Z, Santos-Sacchi J, Nuttall A. Effect of capsaicin on potassium conductance and electromotility of the guinea pig outer hair cell. Hearing Research 2010, 272: 117-124. PMID: 21044673, PMCID: PMC3387680, DOI: 10.1016/j.heares.2010.10.010.Peer-Reviewed Original ResearchConceptsOuter hair cellsTRPV-1 channelsHair cellsPrimary sensory neuronsEffects of capsaicinGuinea pig outer hair cellsSensory neuronsPharmacological actionsCapsaicinPotassium conductancePotent blockerPharmacological propertiesDirect actionNovel actionCochlear amplificationK conductanceAuditory effectsClassic activatorAuditory receptionCellsNociceptionElectromotilityBlockersNew findingsNeuronsCombinatorial Cysteine Mutagenesis Reveals a Critical Intramonomer Role for Cysteines in Prestin Voltage Sensing
Bai JP, Surguchev A, Bian S, Song L, Santos-Sacchi J, Navaratnam D. Combinatorial Cysteine Mutagenesis Reveals a Critical Intramonomer Role for Cysteines in Prestin Voltage Sensing. Biophysical Journal 2010, 99: 85-94. PMID: 20655836, PMCID: PMC2895379, DOI: 10.1016/j.bpj.2010.03.066.Peer-Reviewed Original ResearchConceptsDisulfide bond formationCysteine residuesCysteine residue pairsSingle cysteine residueCysteine mutagenesisTransmembrane proteinSubstitution mutantsSLC26 familyResidue pairsFörster resonance energy transferCharge movementVoltage-dependent charge movementDisulfide interactionsResonance energy transferPrestinProteinMutantsDimer formationResiduesCysteineHair cellsSurface expressionAnion transportersCochlear amplificationWestern blot
2008
Anion Control of Voltage Sensing by the Motor Protein Prestin in Outer Hair Cells
Rybalchenko V, Santos-Sacchi J. Anion Control of Voltage Sensing by the Motor Protein Prestin in Outer Hair Cells. Biophysical Journal 2008, 95: 4439-4447. PMID: 18658219, PMCID: PMC2567960, DOI: 10.1529/biophysj.108.134197.Peer-Reviewed Original ResearchConceptsOuter hair cellsHair cellsCochlear amplificationSLC26 anion transporter familyMotor protein prestinMammalian cochlear amplificationVoltage-sensor charge movementAuditory responsivenessCorti's organAnion transporter familyTransporter familyProtein prestinMolecular motorsCharge movementPrestinOrgansCellsComplicated roleVoltage sensing
2007
Developmental Expression of the Outer Hair Cell Motor Prestin in the Mouse
Abe T, Kakehata S, Kitani R, Maruya S, Navaratnam D, Santos-Sacchi J, Shinkawa H. Developmental Expression of the Outer Hair Cell Motor Prestin in the Mouse. The Journal Of Membrane Biology 2007, 215: 49-56. PMID: 17415610, PMCID: PMC4154540, DOI: 10.1007/s00232-007-9004-5.Peer-Reviewed Original ResearchConceptsLateral membranesOuter hair cellsMouse outer hair cellsMotor protein activitySteady-state levelsKnockout experimentsProtein activityDevelopmental expressionMembrane tensionGenetic modificationConformational fluctuationsCellular mechanismsMotor moleculesMolecular motorsOnset of hearingMorphological estimatesProtein densityEarly maturationQuantitative polymerase chain reactionHair cellsVpkCmDevelopmental dataCochlear amplificationMaturationFull maturation
2006
MANIPULATIONS OF CHLORIDE ION CONCENTRATION IN THE ORGAN OF CORTI ALTER OUTER HAIR CELL ELECTROMOTILITY AND COCHLEAR AMPLIFICATION
ZHENG J, ZOU Y, NUTTALL A, SANTOS-SACCHI J. MANIPULATIONS OF CHLORIDE ION CONCENTRATION IN THE ORGAN OF CORTI ALTER OUTER HAIR CELL ELECTROMOTILITY AND COCHLEAR AMPLIFICATION. 2006, 107-108. DOI: 10.1142/9789812773456_0016.Peer-Reviewed Original ResearchCochlear amplification