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
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 cellsMaturation 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
2018
Seeing the long tail: A novel green fluorescent protein, SiriusGFP, for ultra long timelapse imaging
Zhong S, Rivera-Molina F, Rivetta A, Toomre D, Santos-Sacchi J, Navaratnam D. Seeing the long tail: A novel green fluorescent protein, SiriusGFP, for ultra long timelapse imaging. Journal Of Neuroscience Methods 2018, 313: 68-76. PMID: 30578868, PMCID: PMC9431725, DOI: 10.1016/j.jneumeth.2018.12.008.Peer-Reviewed Original ResearchConceptsSuper-resolution structured illumination microscopyFluorescent proteinNovel green fluorescent proteinGreen fluorescent proteinMembrane proteinsPhotostable variantsCell biologyC-terminusStructured illumination microscopyEGFPProteinConfocal imagingSIM imagingCombination of novelIllumination microscopyKey mutationsKnown mutationsOmp25High intensity excitationMutationsLight intensityCo-operative effectSustained fluorescencePhotobleachingMisfolding
2017
Prestin: Molecular Mechanisms Underlying Outer Hair Cell Electromotility
Santos-Sacchi J, Navaratnam D, Raphael R, Oliver D. Prestin: Molecular Mechanisms Underlying Outer Hair Cell Electromotility. Springer Handbook Of Auditory Research 2017, 62: 113-145. DOI: 10.1007/978-3-319-52073-5_5.Peer-Reviewed Original ResearchOuter hair cellsMammalian inner earOuter Hair Cell ElectromotilityHair cell electromotilitySLC26 familyMolecular mechanismsMembrane lipidsConformational changesMechanical feedback mechanismMolecular motorsTension sensitivityPrestinHair cellsVoltage-sensor charge movementAnion transportersReceptor potentialProteinMolecular conformational changesInner earStructural determinationIntracellular chlorideCharge movementTraffickingFeedback mechanismMechanism
2016
Synaptic Ribbons Require Ribeye for Electron Density, Proper Synaptic Localization, and Recruitment of Calcium Channels
Lv C, Stewart WJ, Akanyeti O, Frederick C, Zhu J, Santos-Sacchi J, Sheets L, Liao JC, Zenisek D. Synaptic Ribbons Require Ribeye for Electron Density, Proper Synaptic Localization, and Recruitment of Calcium Channels. Cell Reports 2016, 15: 2784-2795. PMID: 27292637, PMCID: PMC5334794, DOI: 10.1016/j.celrep.2016.05.045.Peer-Reviewed Original ResearchConceptsNeuromast hair cellsProper synaptic localizationHair cellsSynaptic ribbonsZebrafish genesProper localizationCalcium channelsSynaptic vesiclesSmall vesiclesEnhanced exocytosisFrameshift mutationRibeye proteinsSynaptic localizationVesiclesRelease sitesCellsRibeyeRibbon-like structuresNon-spiking cellsSensory systemsLocalizationGenesExocytosisSimilar numberProtein
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
2010
Combinatorial 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
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