2023
Megahertz 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
Single 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
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
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
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
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
2012
Coupling Molecular Motions of Prestin to Cellular Motility: Effects of Voltage, Chloride and Cytoskeleton
Song L, Santos-Sacchi J. Coupling Molecular Motions of Prestin to Cellular Motility: Effects of Voltage, Chloride and Cytoskeleton. Biophysical Journal 2012, 102: 707a-708a. DOI: 10.1016/j.bpj.2011.11.3840.Peer-Reviewed Original Research
2011
Chloride Dependent Coupling of Molecular to Cellular Mechanics in the Outer Hair Cell of Corti's Organ
Song L, Santos-Sacchi J, Shera C, Olson E. Chloride Dependent Coupling of Molecular to Cellular Mechanics in the Outer Hair Cell of Corti's Organ. AIP Conference Proceedings 2011, 1403: 179-184. DOI: 10.1063/1.3658083.Peer-Reviewed Original ResearchCellular mechanicsConformational changesMotor protein prestinProtein prestinMolecular eventsLateral membranesOHC lateral membraneCellular expressionWhole cellsElectromotilityOuter Hair CellsPrestinHair cellsReceptor potentialNonlinear capacitanceMolecular conformational changesIntracellular chloride levelsCellsTight couplingOrgansOHC receptor potentialsExpressionMembraneNormal levelsVivo
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
2009
Prestin's Anion Transport and Voltage-Sensing Capabilities Are Independent
Bai JP, Surguchev A, Montoya S, Aronson PS, Santos-Sacchi J, Navaratnam D. Prestin's Anion Transport and Voltage-Sensing Capabilities Are Independent. Biophysical Journal 2009, 96: 3179-3186. PMID: 19383462, PMCID: PMC2718310, DOI: 10.1016/j.bpj.2008.12.3948.Peer-Reviewed Original ResearchMeSH Keywords4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAnalysis of VarianceAnimalsAnion Transport ProteinsAntiportersCarbon RadioisotopesChloridesCHO CellsCricetinaeCricetulusElectric CapacitanceFormatesGerbillinaeIon TransportMiceMutation, MissenseOxalatesPatch-Clamp TechniquesSalicylatesSulfate TransportersConceptsClosest phylogenetic relativesTransmembrane regionSLC26 anion transporter familyMammalian outer hair cellsMembrane protein prestinPrestin's motor functionAnion transportPhylogenetic relativesAnion transporter familyTransporter familyProtein prestinChloride-binding siteGating charge movementPrestinCharge movementHair cellsOuter hair cellsResiduesMechanistic conceptsVoltage sensingTransport capabilityCellsVoltage sensorPrevious observationsUptake studies
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
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
On Membrane Motor Activity and Chloride Flux in the Outer Hair Cell: Lessons Learned from the Environmental Toxin Tributyltin
Song L, Seeger A, Santos-Sacchi J. On Membrane Motor Activity and Chloride Flux in the Outer Hair Cell: Lessons Learned from the Environmental Toxin Tributyltin. Biophysical Journal 2004, 88: 2350-2362. PMID: 15596517, PMCID: PMC1305283, DOI: 10.1529/biophysj.104.053579.Peer-Reviewed Original ResearchConceptsLateral membranesCell’s mechanical activityOuter hair cellsMammalian cochlear amplifierHair cellsMembrane motorMarine mammalsIntact outer hair cellsPotent abilityFood chainNonselective conductanceCl(-) homeostasisPrestinNanomolar concentrationsExtracellular Cl- concentrationCl fluxMembraneCellsNew environmental threatsMammalsChloride effectTributyltinEnvironmental threatsHomeostasisNonlinear capacitanceProtein- 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
Voltage-dependent changes in specific membrane capacitance caused by prestin, the outer hair cell lateral membrane motor
Santos-Sacchi J, Navarrete E. Voltage-dependent changes in specific membrane capacitance caused by prestin, the outer hair cell lateral membrane motor. Pflügers Archiv - European Journal Of Physiology 2002, 444: 99-106. PMID: 11976921, DOI: 10.1007/s00424-002-0804-2.Peer-Reviewed Original ResearchConceptsMembrane motorHEK cellsOuter hair cellsArea motor modelLateral membrane areaLateral plasma membranePlasma membraneProtein prestinConstant membrane thicknessConformational changesCharge movementMembrane capacitanceMolecular motorsPrestinMembrane surface areaVoltage sensorDeiters' cellsHair cellsCellsExtreme hyperpolarizationMembrane voltageVoltage-dependent changesMembrane area
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