Affinage

SLC26A5

Prestin · UniProt P58743

Length
744 aa
Mass
81.3 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Prestin (SLC26A5) is the membrane motor protein of cochlear outer hair cells (OHCs) and functions as a direct voltage-to-force converter: heterologous expression confers voltage-induced shape changes and nonlinear capacitance (NLC), and its targeted deletion abolishes OHC electromotility and causes 40–60 dB loss of cochlear sensitivity without disrupting mechano-electrical transduction, establishing it as the molecular basis of the cochlear amplifier (PMID:10821263, PMID:12239568). It is a 7+7 inverted-repeat transmembrane protein with cytoplasmic N- and C-termini that assembles as a swapped dimer—the building block for higher-order oligomers stabilized through the N-terminus and core interactions—where a central cavity serves as the anion-binding/substrate site (PMID:11435925, PMID:16682411, PMID:24710176, PMID:35022426). Intracellular Cl⁻ acts as an obligate cofactor for voltage-dependent motor activity and stiffness (PMID:14534242), and cryo-EM structures bound to chloride, sulfate, or salicylate resolve the mechanism: the bound anion together with coordinating charged residues acts as a dynamic voltage sensor whose conformational transitions are allosterically coupled to changes in transmembrane cross-sectional area and surrounding membrane deformation, producing the area change that drives somatic motility (PMID:34390643, PMID:34695838, PMID:36266333, PMID:24554714). Prestin's residual weak anion transport (formate, oxalate, Cl⁻/HCO₃⁻ and Cl⁻/SO₄²⁻ exchange, SCN⁻ flux) reflects an ancestral SLC26 transport cycle and is mechanistically separable from voltage sensing, and in vivo it is the fast motor kinetics—not anion transport—that is essential for mammalian cochlear amplification (PMID:17442754, PMID:19383462, PMID:21701557, PMID:36893263). Its surface expression and operating voltage are tuned by N-glycosylation at N163/N166, calcium-obligate calmodulin binding to a C-terminal disordered region, membrane cholesterol and lipid-raft localization, and interaction with partners MAP1S (enhancing trafficking) and CFTR (augmenting charge displacement upon cAMP activation) (PMID:15140192, PMID:20418376, PMID:20138822, PMID:24453323, PMID:17321873). Beyond the cochlea, prestin is expressed in cardiac myocytes where it amplifies actin-myosin force generation (PMID:33951436).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 High

    Established the molecular identity of the OHC motor by showing a single protein converts voltage into mechanical force, resolving the long-standing question of what powers OHC electromotility.

    Evidence Heterologous expression in HEK cells with voltage-clamp NLC and motility assay; developmental immunolocalization tied to onset of electromotility

    PMID:10821263 PMID:11125015

    Open questions at the time
    • Did not resolve oligomeric state or atomic structure
    • Mechanism of voltage-to-area coupling unknown at this stage
  2. 2002 High

    Demonstrated prestin is necessary in vivo for the cochlear amplifier, distinguishing its motor role from mechano-electrical transduction.

    Evidence Prestin knockout mouse with in vitro electromotility and in vivo ABR thresholds

    PMID:12239568

    Open questions at the time
    • Whole-animal loss does not isolate which biophysical property (kinetics vs transport) is essential
    • No structural basis provided
  3. 2003 High

    Showed prestin localization to the OHC basolateral membrane and that intracellular Cl⁻ is an obligate cofactor for voltage-dependent stiffness and motility, defining the anion requirement of the motor.

    Evidence Voltage-clamp of guinea pig OHCs with intracellular Cl⁻ perfusion and axial stiffness measurement; comparative localization in cytoplasmic vestibular hair cells lacking electromotility

    PMID:14534242 PMID:14553901

    Open questions at the time
    • Whether Cl⁻ is a true voltage sensor or modulator was not settled
    • Structural location of the anion site unknown
  4. 2005 Medium

    Mapped topology and trafficking determinants, identifying cytoplasmic termini and C-terminal residues required for membrane targeting and voltage sensing.

    Evidence Truncation/point/chimeric mutagenesis with NLC and immunofluorescence; FRET demonstrating N-terminal homo-oligomerization

    PMID:11435925 PMID:15976456 PMID:16113116

    Open questions at the time
    • Single-lab topology models later revised by cryo-EM
    • Precise targeting sequence mechanism not resolved
  5. 2006 High

    Defined prestin's quaternary organization as a disulfide-stabilized dimer assembling into higher-order oligomers, the structural unit of the motor.

    Evidence LDS/PFO-PAGE, chemical cross-linking, membrane yeast two-hybrid, affinity purification, and FRET in native OHCs and HEK cells

    PMID:16626645 PMID:16682411

    Open questions at the time
    • Functional necessity of oligomerization for motility not fully resolved here
    • Whether subunits act cooperatively unknown
  6. 2009 High

    Separated prestin's anion transport from its voltage-sensing/motor function, showing point mutations abolish transport while preserving NLC.

    Evidence Radioactive formate/oxalate uptake assays with site-directed mutagenesis and patch-clamp in heterologous cells

    PMID:19383462

    Open questions at the time
    • Physiological role of residual transport in vivo unresolved at this stage
    • Did not establish the structural coupling between transport cycle and motility
  7. 2007 High

    Linked mammalian electromotility to an ancestral SLC26 anion-exchange cycle by characterizing non-mammalian prestin orthologs as electrogenic anion exchangers.

    Evidence Patch-clamp of chicken/zebrafish prestin with stoichiometry from reversal potentials and salicylate pharmacology; FRET/Co-IP of prestin homomers and prestin-GLUT5 heteromers

    PMID:17442754 PMID:17443803

    Open questions at the time
    • Evolutionary transition from transporter to motor not mechanistically mapped
    • Functional role of prestin-GLUT5 heteromers unclear
  8. 2010 High

    Resolved the STAS domain structure and identified protein partners (MAP1S, CFTR) that regulate prestin trafficking and charge displacement.

    Evidence X-ray crystallography (1.57 Å) and NMR of STAS; yeast two-hybrid, reciprocal Co-IP, FRET and electrophysiology for MAP1S and CFTR with prestin-KO controls

    PMID:20138822 PMID:20418376 PMID:20471983

    Open questions at the time
    • How STAS-partner interactions are regulated in vivo unknown
    • Stoichiometry of partner complexes not determined
  9. 2011 High

    Established electromotility as a two-step process (anion-binding alternate-access transition followed by an electromotility-generating transition) using domain-swap chimeras.

    Evidence Synthetic chimeric prestin (SynPres) with heterologous expression, NLC and anion transport assays

    PMID:21701557

    Open questions at the time
    • Structural identity of the two transmembrane core domains not resolved here
    • Kinetics of the intermediary transition undefined
  10. 2014 Medium

    Localized the anion/substrate site to a central cavity in a 7+7 inverted-repeat architecture and identified calmodulin as a calcium-obligate C-terminal regulator.

    Evidence Homology modeling with SCAM cysteine-accessibility and mutagenesis; CaM binding assays with patch-clamp in OHCs and heterologous cells; area-motor biophysics from chloride/salicylate manipulation

    PMID:24453323 PMID:24554714 PMID:24710176 PMID:24901231

    Open questions at the time
    • Modeled architecture awaited experimental cryo-EM confirmation
    • Physiological trigger for CaM modulation in vivo unknown
  11. 2016 Medium

    Refined the role of chloride, showing it controls prestin kinetics rather than total voltage-sensor charge Qmax, revising the extrinsic-voltage-sensor view.

    Evidence Multifrequency admittance and displacement current integration with OHC electromotility and voltage-clamp; earlier kinetic modeling of an intermediary 'transporter legacy' gateway

    PMID:23431177 PMID:27276272

    Open questions at the time
    • Molecular nature of the intermediary transition unresolved
    • Single-lab biophysical reinterpretation
  12. 2021 High

    Provided the structure-based mechanism by resolving prestin cryo-EM structures in multiple ligand-bound states, showing anion-site conformational changes coupled to transmembrane area and membrane deformation.

    Evidence Single-particle cryo-EM of human and dolphin prestin in multiple states with MD simulations and patch-clamp; KO demonstration of a cardiac actin-myosin force-amplifying role

    PMID:33951436 PMID:34390643 PMID:34695838

    Open questions at the time
    • Dynamic transition rates between states not directly measured
    • Cardiac mechanism and partners only partially characterized
  13. 2022 High

    Refined the dimeric mechanism, showing swapped-dimer architecture, rigid-body core/gate movements, and that dimer-interface stabilization is required for NLC, while chloride-site mutation retains NLC—challenging the extrinsic voltage-sensor hypothesis.

    Evidence Cryo-EM of gerbil and thermostabilized prestin in chloride/sulfate/salicylate states with dimeric-interface and chloride-site mutagenesis and NLC readouts

    PMID:35022426 PMID:36266333

    Open questions at the time
    • Reconciliation of intrinsic vs anion-dependent voltage sensing incomplete
    • Lipid/membrane organization role inferred mainly from simulation (#37)
  14. 2023 High

    Definitively separated motor kinetics from anion transport in vivo, showing fast prestin kinetics—not weak anion transport—is essential for cochlear amplification.

    Evidence Knockin mice with a slowed prestin variant and a transport-disrupting mutation, assessed by ABR/DPOAE and electromotility

    PMID:36893263

    Open questions at the time
    • Physiological function (if any) of residual anion transport in mammals remains undefined
    • Upstream determinants setting motor kinetics in vivo not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How prestin conformational kinetics, lipid/membrane organization, and partner/post-translational regulation are integrated to set cochlear amplifier gain in vivo remains incompletely defined.
  • Direct in vivo measurement of state-transition rates lacking
  • Membrane-mediated dimer organization rests on simulation (#37)
  • Cardiac role mechanistically underexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0140299 molecular sensor activity 5 GO:0005198 structural molecule activity 3
Localization
GO:0005829 cytosol 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-382551 Transport of small molecules 4 R-HSA-112316 Neuronal System 3
Partners
CALM1CFTRGLUT5MAP1S

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Prestin (SLC26A5) is the motor protein of cochlear outer hair cells; heterologous expression in kidney cells confers voltage-induced shape changes and nonlinear capacitance, demonstrating it is a direct voltage-to-force converter. Heterologous expression in HEK cells, voltage-clamp electrophysiology (nonlinear capacitance), outer hair cell motility assay Nature High 10821263
2002 Targeted deletion of prestin in mice abolishes outer hair cell electromotility in vitro and causes 40–60 dB loss of cochlear sensitivity in vivo, without disrupting mechano-electrical transduction, establishing prestin as essential for the cochlear amplifier. Prestin knockout mouse, in vitro electromotility recording, in vivo auditory threshold measurement (ABR) Nature High 12239568
2000 Prestin protein incorporation into the outer hair cell lateral plasma membrane begins from postnatal day 0 and increases progressively, with its time course coinciding with development of electromotility, while GLUT-5 is not incorporated into the lateral membrane until postnatal day 15, supporting prestin (not GLUT-5) as the fundamental motor component. Immunofluorescence with specific antibodies, patch-clamp recording of transient charge movement during postnatal development The Journal of Neuroscience High 11125015
2001 Prestin's N- and C-termini are cytoplasmic, as determined by epitope-tag immunofluorescence under permeabilizing and non-permeabilizing conditions in transfected cells. Epitope-tagged constructs, immunofluorescence in permeabilized vs. non-permeabilized transfected cells Neuroreport Medium 11435925
2005 Prestin is a 10-transmembrane domain protein with both intracellular termini required for normal voltage sensing; short truncations of either terminus eliminate or modify activity despite normal membrane targeting. The N-terminus mediates prestin homo-oligomerization, as shown by FRET. Truncation/deletion mutagenesis, nonlinear capacitance electrophysiology, FRET between fluorescently tagged prestin constructs Biophysical Journal Medium 16113116
2006 Prestin forms stable homo-oligomers (likely tetramers) in native outer hair cells and heterologous expression systems; the dimer is stabilized by a disulfide bond in the hydrophobic core, and the dimer serves as the building block for higher-order oligomers. LDS-PAGE, perfluoro-octanoate-PAGE, membrane-based yeast two-hybrid, chemical cross-linking, affinity purification The Journal of Biological Chemistry High 16682411
2006 Self-association of prestin in HEK cell membranes demonstrated by FRET (acceptor photobleach and sensitized emission), with average FRET efficiency ~9–10%, confirming prestin-prestin interactions. Acceptor photobleach FRET and sensitized emission FRET with CFP/YFP-tagged prestin in HEK cells Brain Research Medium 16626645
2005 The C-terminus of prestin (nearly full length, >708 amino acids required) controls plasma membrane targeting and nonlinear capacitance function; specific residues Y520 and Y526 are implicated in basolateral targeting, and V499/Y501 affect function without disrupting membrane expression. Series of deletion, point, and chimeric mutants expressed heterologously; nonlinear capacitance measurement; immunofluorescence Journal of Cell Science Medium 15976456
2004 Prestin is N-glycosylated at N163 and N166; N-linked glycosylation is not required for plasma membrane targeting but deglycosylation shifts the voltage of peak charge transfer to more depolarized values, quantitatively affecting OHC electromotility. Site-directed mutagenesis of glycosylation sites, tunicamycin/glycopeptidase-F treatment, SDS-PAGE, electrophysiology (nonlinear capacitance) Journal of Neurochemistry High 15140192
2007 Non-mammalian prestin orthologs (chicken, zebrafish) are electrogenic divalent/chloride anion exchangers (1:1 SO4²⁻/Cl⁻ antiport), blocked by salicylate, revealing that mammalian prestin's electromotility mechanism is closely related to an ancestral anion transport cycle. Patch-clamp recordings in heterologously expressed chicken/zebrafish prestin; determination of transport stoichiometry from reversal potentials under defined ion gradients Proceedings of the National Academy of Sciences High 17442754
2003 Prestin is specifically expressed in the basolateral (lateral) plasma membrane of outer hair cells; intracellular Cl⁻ acts as an extrinsic voltage sensor: removal of intracellular Cl⁻ eliminates voltage-dependent stiffness and electromotility, showing motor protein stiffness is a major contributor to axial stiffness of OHCs. Whole-cell voltage-clamp of isolated guinea pig OHCs; axial stiffness measurement by calibrated fiber; Cl⁻ removal via intracellular perfusion The Journal of Neuroscience High 14534242
2005 cGMP (via PKG) modulates prestin's voltage-dependent charge displacement more strongly than cAMP; mutagenesis of two PKG phosphorylation sites on prestin shows they interact and one may influence prestin's membrane targeting. Cyclic nucleotide application to prestin-transfected TSA201 cells; site-directed mutagenesis of S/T phosphorylation sites (alanine/aspartate substitutions); nonlinear capacitance recording; confocal microscopy The Journal of Physiology Medium 15649974
2010 Crystal structure (1.57 Å) of the cytosolic STAS domain of prestin reveals it begins immediately after the last transmembrane segment and lies beneath the lipid bilayer; disease-associated mutations either cause STAS misfolding or alter interaction surfaces. X-ray crystallography, heteronuclear multidimensional NMR spectroscopy, mutational analysis Journal of Molecular Biology High 20471983
2009 Mammalian prestin transports anions (formate, oxalate) comparable to SLC26A6; mutations P328A and L326A preserve nonlinear capacitance but abolish anion transport, distinguishing the transport and voltage-sensing functions; 12 of 22 charged transmembrane residues contribute to unitary charge movement. Radioactive anion uptake assays (¹⁴C-formate, ¹⁴C-oxalate), site-directed mutagenesis, patch-clamp electrophysiology Biophysical Journal High 19383462
2010 CFTR co-localizes with prestin in the lateral membrane of OHCs (but not in IHCs or prestin-knockout OHCs), physically interacts with prestin (confirmed by co-immunoprecipitation), and cAMP-activated CFTR enhances voltage-dependent charge displacement of prestin. In situ hybridization, immunofluorescence, co-immunoprecipitation, whole-cell patch-clamp electrophysiology in OHCs and transfected cells Biochimica et Biophysica Acta High 20138822
2010 MAP1S (microtubule-associated protein 1S) binds to the STAS domain of prestin; co-expression with MAP1S increases prestin surface expression 2.8-fold and charge density 2.7-fold, showing MAP1S augments prestin activity by promoting surface trafficking. Yeast two-hybrid, reciprocal immunoprecipitation, FRET, quantitative PCR, electrophysiology (charge density measurement) The Journal of Biological Chemistry High 20418376
2011 A synthetic chimeric prestin (SynPres) combining mammalian and non-mammalian prestin domains shows that two distinct transmembrane core domains are necessary and sufficient for electromotility/NLC; the amplitude of NLC is determined by monovalent anion transport, indicating electromotility is a dual-step process: anion transport by an alternate-access cycle followed by an anion-dependent electromotility-generating transition. Chimeric protein construction, heterologous expression, patch-clamp electrophysiology (NLC), anion transport assay The EMBO Journal High 21701557
2014 The structural model of prestin's transmembrane core has a 7+7 inverted repeat architecture with a central cavity as the anion-binding/substrate site; cysteine accessibility scanning and mutagenesis confirm the central cavity is the substrate-binding site controlling electromotile activity. Homology modeling, MD simulations, cysteine accessibility scanning (SCAM), mutational analysis of electromotility Nature Communications Medium 24710176
2014 Calmodulin (CaM) binds directly to an intrinsically disordered region (IDR) in prestin's C-terminal domain in a calcium-obligate manner; this CaM binding shifts the operating point of prestin to more hyperpolarized potentials, modulating its function. Bioinformatic prediction, biochemical binding assays, patch-clamp electrophysiology in isolated OHCs and heterologous cells The Journal of Neuroscience High 24453323
2021 Cryo-EM structures of human prestin bound with chloride (contracted state) or salicylate (expanded state) at a common anion site reveal that conformational changes in the anion-binding site are allosterically coupled to changes in transmembrane domain cross-sectional area and surrounding membrane deformation, providing a structure-based mechanism for OHC electromotility. Cryo-electron microscopy, computational molecular dynamics simulations, functional assays Cell High 34390643
2021 Single-particle cryo-EM of dolphin prestin in six distinct states shows that bound anion identity (Cl⁻ vs SO₄²⁻) tunes prestin conformational states; salicylate competes for the anion-binding site and immobilizes prestin in a new conformation; the anion together with coordinating charged residues and helical dipole act as a dynamic voltage sensor; structural rearrangements at the voltage sensor couple to area expansion at the protein-membrane interface. Single-particle cryo-EM (six states), patch-clamp electrophysiology, pharmacological characterization Nature High 34695838
2022 Cryo-EM structure of gerbil prestin at 3.6 Å reveals it forms a swapped dimer with 14 TM segments in two 7+7 inverted repeats; captured in an inward-open (contracted) state; mutation of the chloride-binding site removes salicylate competition with anions while retaining NLC, undermining the extrinsic voltage sensor hypothesis. Single-particle cryo-EM, site-directed mutagenesis of chloride-binding site, patch-clamp electrophysiology Nature Communications High 35022426
2022 Cryo-EM structures of thermostabilized prestin with chloride, sulfate, or salicylate show rigid-body movement between core and gate domains; mutations at the dimeric interface severely diminish NLC, indicating gate domain stabilization facilitates core domain movement for NLC expression. Cryo-EM, site-directed mutagenesis of dimeric interface, patch-clamp electrophysiology (NLC) Nature Communications High 36266333
2012 The V499G/Y501H mutation (with V499 as the primary site) impairs fast motor kinetics and voltage operating range of prestin without eliminating voltage-induced motor activity; V499G/Y501H prestin forms heteromers with wild-type prestin but does not dominantly impair wild-type kinetics, suggesting prestin subunits function independently within a multimer. Site-directed mutagenesis, patch-clamp electrophysiology (NLC kinetics), heteromeric co-expression The Journal of Biological Chemistry High 23212912
2007 Prestin-prestin homomeric interactions and prestin-GLUT5 heteromeric interactions in OHC-relevant cell models, confirmed by membrane co-localization, FRET (FACS, acceptor photobleaching, FLIM), and co-immunoprecipitation. Confocal co-localization, FRET by FACS/acceptor photobleaching/FRET-FLIM, co-immunoprecipitation in HEK293T cells Developmental Neurobiology Medium 17443803
2008 Membrane cholesterol modulates prestin-associated nonlinear capacitance: increasing cholesterol causes a hyperpolarizing shift in peak voltage (Vpkc) and decreases total charge movement linearly; docosahexaenoic acid causes a hyperpolarizing shift with increased charge movement. Cholesterol/DHA loading of HEK293 cells expressing prestin, patch-clamp electrophysiology (NLC) The Journal of Biological Chemistry Medium 18567583
2007 Prestin localizes to membrane microdomains (lipid rafts) in HEK293 cells; depletion of membrane cholesterol alters prestin localization and reduces nonlinear capacitance, showing that microdomain localization is required for full prestin activity. Immunocolocalization, sucrose density gradient fractionation, cholesterol depletion, patch-clamp (NLC) Otolaryngology–Head and Neck Surgery Medium 17321873
2009 Glycosylation regulates prestin self-association and cellular trafficking; the non-glycosylated double mutant prestin(NN163/166AA) is enriched as monomers and more mobile in the plasma membrane; oligomerization depends on glycosylation but is not essential for NLC in HEK293 cells; in the presence of increased cholesterol, non-glycosylated prestin shows cholesterol-dependent decrease in surface expression and loss of NLC. Glycosylation site mutagenesis, cholesterol manipulation, flow cytometry, confocal microscopy, patch-clamp (NLC) Journal of the Association for Research in Otolaryngology Medium 19898896
2012 Rat prestin mediates SCN⁻ transport currents (electrogenic) proportional to prestin expression level, establishing that mammalian prestin retains electrogenic anion transport capability; comparison with zebrafish prestin and SLC26A7 shows SCN⁻ transport is conserved in the SLC26 family. Heterologous expression, patch-clamp recording, variation of SCN⁻ concentration, noise analysis The Journal of Physiology Medium 22063625
2012 Mammalian prestin acts as a weak Cl⁻/HCO₃⁻ electrogenic antiporter; HCO₃⁻ transport by prestin-transfected cells was demonstrated by accelerated recovery from acid load and shift in reversal potential, requiring a chloride gradient. Intracellular pH sensor (pHluorin, BCECF), whole-cell patch-clamp, heterologous expression and OHC recordings The Journal of Physiology Medium 22890707
2013 Disparities between prestin's voltage-sensor charge movement (NLC) and electromotility as a function of intracellular chloride reveal that chloride drives slow state transitions; a kinetic model with fast anion-binding and fast voltage-dependent transitions coupled by a slower intermediary transition recapitulates the data, suggesting an intermediary 'transporter legacy' gateway. Simultaneous NLC and electromotility measurement, whole-cell patch-clamp, kinetic modeling Proceedings of the National Academy of Sciences Medium 23431177
2021 Prestin (Slc26a5) is expressed in cardiac myocytes and amplifies actin-myosin force generation; prestin-knockout mice show significant alterations in cardiac contractility, establishing a motor function of prestin beyond the inner ear. Prestin-KO mouse model, cardiac contractility measurements, electrophysiology (nonlinear capacitance in cardiomyocytes) Cell Reports Medium 33951436
2023 Restoring fast motor kinetics in mice expressing a slowed prestin missense variant rescues cochlear amplification, demonstrating that prestin's fast motor kinetics is essential for mammalian cochlear amplification; the anion transport-disrupting point mutation does not alter cochlear function, suggesting weak anion transport of prestin is not essential in the mammalian cochlea. Knockin mouse model (slowed prestin variant), auditory function tests (ABR/DPOAE), electromotility measurements Proceedings of the National Academy of Sciences High 36893263
2003 Prestin is expressed in vestibular hair cells of rodents, but is localized to the cytoplasm (not lateral plasma membrane) in vestibular hair cells and does not produce voltage-dependent capacitance; OHC-type somatic electromotility is absent in vestibular hair cells despite prestin expression. RT-PCR, in situ hybridization, immunolocalization, whole-cell patch-clamp in vestibular hair cells Hearing Research Medium 14553901
2010 Prestin is expressed on the whole OHC basolateral membrane including the basal pole (not just lateral wall), though staining is weaker at the base; prestin is absent from the cuticular plate, stereocilia, cytoplasm, and nuclei. Immunofluorescence with confocal microscopy, co-staining with membrane dye di-8-ANEPPS, hypotonic challenge to separate membrane layers in mouse/rat/guinea pig OHCs Brain Research Medium 16709400
2007 A single point mutation A100W in prestin eliminates prestin-associated charge movement and diminishes electromechanical force generation in membrane tethers without altering passive membrane mechanics, demonstrating that prestin-associated charge transfer is required for maximal electromechanical force. Site-directed mutagenesis, membrane tether pulling from HEK cells, optical tweezers measurement of electromechanical force Biophysical Journal Medium 17468166
2018 Charged residues in the extracellular loop of prestin (and pendrin) play significant roles in setting the voltage-operating points of nonlinear capacitance; pendrin also exhibits large NLC, suggesting voltage sensing is not unique to prestin within SLC26 and works independently of anion transport. Site-directed mutagenesis of extracellular loop charged residues, patch-clamp electrophysiology (NLC) in transfected cells The Journal of Biological Chemistry Medium 29777056
2022 Coarse-grained MD simulations show prestin causes anisotropic membrane deformation that mediates preferential lateral organization of prestin dimers with constructively aligned deformation patterns, reducing membrane rigidity and hypothesized to maximize OHC reshaping. Coarse-grained molecular dynamics simulations (>0.5 ms collective sampling) Nature Communications Low 36371434
2014 Chloride and salicylate manipulations show that the outer hair cell motor produces voltage-dependent changes in membrane surface area (area motor model); unit linear motor capacitance fluctuation is ~140 zeptofarads, and salicylate augments this by locking motors in the expanded state. Whole-cell patch-clamp with simultaneous nonlinear and linear capacitance measurements, chloride and salicylate manipulation The Journal of Biological Chemistry Medium 24554714
2016 Chloride controls prestin kinetics (and hence apparent charge magnitude at any given frequency) but not the total voltage-sensor charge Qmax; as interrogation frequency decreases, Qmax asymptotes to a level independent of chloride concentration. Multifrequency admittance, expanded displacement current integration, OHC electromotility measurement, whole-cell voltage-clamp Biophysical Journal Medium 27276272
2014 Gerbil prestin (SLC26A5) mediates physiological (mM-range) chloride flux in HEK cells expressing the protein, demonstrated using a novel chloride-sensitive YFP sensor fused to prestin. Genetically encoded chloride indicator (monomeric Cl-YFP) fused to prestin, fluorescence-based Cl⁻ flux assay in HEK cells PLoS ONE Medium 24901231

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Prestin is the motor protein of cochlear outer hair cells. Nature 954 10821263
2002 Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier. Nature 672 12239568
2006 Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and hepatocarcinogenesis. Cancer science 230 16863502
2014 Hepatitis B virus PreS/S gene variants: pathobiology and clinical implications. Journal of hepatology 219 24801416
2002 Prestin, a new type of motor protein. Nature reviews. Molecular cell biology 212 11836512
2008 Cochlear amplification, outer hair cells and prestin. Current opinion in neurobiology 203 18809494
2000 Expression and localization of prestin and the sugar transporter GLUT-5 during development of electromotility in cochlear outer hair cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 183 11125015
1987 Expression of hepatitis B virus surface and core antigens: influences of pre-S and precore sequences. Journal of virology 165 3543403
2010 The hearing gene Prestin unites echolocating bats and whales. Current biology : CB 146 20129037
2003 Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss. Human molecular genetics 144 12719379
2012 Impact of hepatitis B virus (HBV) preS/S genomic variability on HBV surface antigen and HBV DNA serum levels. Hepatology (Baltimore, Md.) 118 22271491
2008 Ground glass hepatocytes contain pre-S mutants and represent preneoplastic lesions in chronic hepatitis B virus infection. Journal of gastroenterology and hepatology 117 18505413
2008 The hearing gene Prestin reunites echolocating bats. Proceedings of the National Academy of Sciences of the United States of America 96 18776049
2006 Prestin and the cochlear amplifier. The Journal of physiology 96 16873410
2005 N-terminal-mediated homomultimerization of prestin, the outer hair cell motor protein. Biophysical journal 87 16113116
2007 Nonmammalian orthologs of prestin (SLC26A5) are electrogenic divalent/chloride anion exchangers. Proceedings of the National Academy of Sciences of the United States of America 81 17442754
2006 Analysis of the oligomeric structure of the motor protein prestin. The Journal of biological chemistry 81 16682411
2012 Posterior reversible encephalopathy syndrome (PRES): features on CT and MR imaging. Diagnostic and interventional imaging 74 22835573
2001 Prestin topology: localization of protein epitopes in relation to the plasma membrane. Neuroreport 73 11435925
2007 Developmental expression of the outer hair cell motor prestin in the mouse. The Journal of membrane biology 71 17415610
2021 Molecular mechanism of prestin electromotive signal amplification. Cell 70 34390643
2008 Prestin up-regulation in chronic salicylate (aspirin) administration: an implication of functional dependence of prestin expression. Cellular and molecular life sciences : CMLS 67 18560754
2021 The conformational cycle of prestin underlies outer-hair cell electromotility. Nature 65 34695838
2013 Prestin regulation and function in residual outer hair cells after noise-induced hearing loss. PloS one 65 24376553
2005 The C-terminus of prestin influences nonlinear capacitance and plasma membrane targeting. Journal of cell science 64 15976456
2014 Molecular architecture and the structural basis for anion interaction in prestin and SLC26 transporters. Nature communications 62 24710176
2009 Prestin's anion transport and voltage-sensing capabilities are independent. Biophysical journal 62 19383462
2003 Prestin and the dynamic stiffness of cochlear outer hair cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 62 14534242
2005 Effects of cyclic nucleotides on the function of prestin. The Journal of physiology 59 15649974
2004 N-linked glycosylation sites of the motor protein prestin: effects on membrane targeting and electrophysiological function. Journal of neurochemistry 55 15140192
2003 Expression of prestin, a membrane motor protein, in the mammalian auditory and vestibular periphery. Hearing research 54 14553901
2010 Structure of the cytosolic portion of the motor protein prestin and functional role of the STAS domain in SLC26/SulP anion transporters. Journal of molecular biology 53 20471983
2002 Prestin, the motor protein of outer hair cells. Audiology & neuro-otology 51 11914518
2015 PRES in Children Undergoing Hematopoietic Stem Cell or Solid Organ Transplantation. Pediatrics 50 25917987
2003 Identification and characterization of polyhomeotic PREs and TREs. Developmental biology 49 14499651
2003 Expression of prestin-homologous solute carrier (SLC26) in auditory organs of nonmammalian vertebrates and insects. Proceedings of the National Academy of Sciences of the United States of America 48 12782792
2021 Clinical Implications of HBV PreS/S Mutations and the Effects of PreS2 Deletion on Mitochondria, Liver Fibrosis, and Cancer Development. Hepatology (Baltimore, Md.) 47 33675094
2006 Prestin is expressed on the whole outer hair cell basolateral surface. Brain research 45 16709400
2014 A genetically-encoded YFP sensor with enhanced chloride sensitivity, photostability and reduced ph interference demonstrates augmented transmembrane chloride movement by gerbil prestin (SLC26a5). PloS one 44 24901231
2022 Single particle cryo-EM structure of the outer hair cell motor protein prestin. Nature communications 43 35022426
2013 Prestin at year 14: progress and prospect. Hearing research 42 24361298
2003 Genomic characterization and expression of mouse prestin, the motor protein of outer hair cells. Mammalian genome : official journal of the International Mammalian Genome Society 42 12584604
2010 Interaction between CFTR and prestin (SLC26A5). Biochimica et biophysica acta 41 20138822
2016 Outer Hair Cell Molecular Protein, Prestin, as a Serum Biomarker for Hearing Loss: Proof of Concept. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 39 27636386
2011 A synthetic prestin reveals protein domains and molecular operation of outer hair cell piezoelectricity. The EMBO journal 39 21701557
2012 Outer hair cell-specific prestin-CreERT2 knockin mouse lines. Genesis (New York, N.Y. : 2000) 36 21954035
2008 Membrane composition modulates prestin-associated charge movement. The Journal of biological chemistry 35 18567583
2009 Long-term administration of salicylate enhances prestin expression in rat cochlea. International journal of audiology 34 19173110
2012 The V499G/Y501H mutation impairs fast motor kinetics of prestin and has significance for defining functional independence of individual prestin subunits. The Journal of biological chemistry 33 23212912
2010 Targeting of the hair cell proteins cadherin 23, harmonin, myosin XVa, espin, and prestin in an epithelial cell model. The Journal of neuroscience : the official journal of the Society for Neuroscience 33 20505086
1987 Expression of pre-S gene-encoded proteins in liver and serum during chronic hepatitis B virus infection in comparison to other markers of active virus replication. Journal of hepatology 33 3429833
2013 Disparities in voltage-sensor charge and electromotility imply slow chloride-driven state transitions in the solute carrier SLC26a5. Proceedings of the National Academy of Sciences of the United States of America 32 23431177
2006 Assessment of prestin self-association using fluorescence resonance energy transfer. Brain research 32 16626645
2015 Therapy and differential diagnosis of posterior reversible encephalopathy syndrome (PRES) during pregnancy and postpartum. Archives of gynecology and obstetrics 28 26122264
2007 Functional expression and microdomain localization of prestin in cultured cells. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 28 17321873
2022 Cryo-EM structures of thermostabilized prestin provide mechanistic insights underlying outer hair cell electromotility. Nature communications 27 36266333
2011 Anion transport by the cochlear motor protein prestin. The Journal of physiology 27 22063625
2022 Noise exposure levels predict blood levels of the inner ear protein prestin. Scientific reports 26 35064195
2017 Changes in Serum Prestin Concentration After Exposure to Cisplatin. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 26 29065096
2013 IR laser-induced perturbations of the voltage-dependent solute carrier protein SLC26a5. Biophysical journal 26 24138858
2012 Ion and solute transport by Prestin in Drosophila and Anopheles. Journal of insect physiology 26 22321763
2010 Prestin and the cholinergic receptor of hair cells: positively-selected proteins in mammals. Hearing research 26 20056140
2005 High frequency of the IVS2-2A>G DNA sequence variation in SLC26A5, encoding the cochlear motor protein prestin, precludes its involvement in hereditary hearing loss. BMC medical genetics 26 16086836
2012 Mammalian prestin is a weak Cl⁻/HCO₃⁻ electrogenic antiporter. The Journal of physiology 25 22890707
2009 Glycosylation regulates prestin cellular activity. Journal of the Association for Research in Otolaryngology : JARO 24 19898896
2022 Vaccine based on folded receptor binding domain-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants. Allergy 23 35357709
2014 Functional regulation of the SLC26-family protein prestin by calcium/calmodulin. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 24453323
2016 Chloride Anions Regulate Kinetics but Not Voltage-Sensor Qmax of the Solute Carrier SLC26a5. Biophysical journal 21 27276272
2010 Prestin surface expression and activity are augmented by interaction with MAP1S, a microtubule-associated protein. The Journal of biological chemistry 21 20418376
2007 A new mutation in the human pres gene and its effect on prestin function. International journal of molecular medicine 21 17786286
2021 Prestin amplifies cardiac motor functions. Cell reports 20 33951436
2021 Hepatitis B Virus Pre-S Gene Deletions and Pre-S Deleted Proteins: Clinical and Molecular Implications in Hepatocellular Carcinoma. Viruses 20 34066744
2016 HEI-OC1 cells as a model for investigating prestin function. Hearing research 20 26854618
2011 Prestin and high frequency hearing in mammals. Communicative & integrative biology 20 21655450
2007 Prestin-prestin and prestin-GLUT5 interactions in HEK293T cells. Developmental neurobiology 20 17443803
2007 Prestin modulates mechanics and electromechanical force of the plasma membrane. Biophysical journal 20 17468166
2017 Posterior reversible encephalopathy syndrome (PRES) induced by pazopanib, a multi-targeting tyrosine kinase inhibitor, in a patient with soft-tissue sarcoma: case report and review of the literature. Investigational new drugs 19 29067537
2013 Lizard and frog prestin: evolutionary insight into functional changes. PloS one 19 23342145
2007 Expression, purification and characterisation of the C-terminal STAS domain of the SLC26 anion transporter prestin. Protein expression and purification 19 18226918
1999 Identification and expression of glycine decarboxylase (p120) as a duck hepatitis B virus pre-S envelope-binding protein. The Journal of biological chemistry 19 10488106
2019 Prestin kinetics and corresponding frequency dependence augment during early development of the outer hair cell within the mouse organ of Corti. Scientific reports 18 31712635
2014 Chloride and salicylate influence prestin-dependent specific membrane capacitance: support for the area motor model. The Journal of biological chemistry 18 24554714
2015 Activity-dependent regulation of prestin expression in mouse outer hair cells. Journal of neurophysiology 17 25810486
2006 En block C-terminal charge cluster reversals in prestin (SLC26A5): effects on voltage-dependent electromechanical activity. Neuroscience letters 17 16839688
2023 Prestin's fast motor kinetics is essential for mammalian cochlear amplification. Proceedings of the National Academy of Sciences of the United States of America 16 36893263
2022 HBV preS Mutations Promote Hepatocarcinogenesis by Inducing Endoplasmic Reticulum Stress and Upregulating Inflammatory Signaling. Cancers 16 35805045
2014 Chloride-driven electromechanical phase lags at acoustic frequencies are generated by SLC26a5, the outer hair cell motor protein. Biophysical journal 16 24988347
2001 Cloning, expression, and purification of histidine-tagged preS domains of hepatitis B virus. Protein expression and purification 16 11162405
2021 Prestin and otolin-1 proteins in the hearing loss of adults chronically exposed to lead. Toxicology and applied pharmacology 15 34273409
2018 The extracellular loop of pendrin and prestin modulates their voltage-sensing property. The Journal of biological chemistry 15 29777056
2022 Mutations in the HBV PreS/S gene related to hepatocellular carcinoma in Vietnamese chronic HBV-infected patients. PloS one 14 35390033
2022 Lipid-mediated prestin organization in outer hair cell membranes and its implications in sound amplification. Nature communications 14 36371434
2019 Voltage Does Not Drive Prestin (SLC26a5) Electro-Mechanical Activity at High Frequencies Where Cochlear Amplification Is Best. iScience 14 31812809
1999 Expression and characterization of chimeric hepatitis B surface antigen particles carrying preS epitopes. Journal of biotechnology 14 10406098
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. The Journal of neuroscience : the official journal of the Society for Neuroscience 13 36868859
2021 Prestin and electromotility may serve multiple roles in cochlear outer hair cells. Hearing research 13 34987016
2016 Synchronized Progression of Prestin Expression and Auditory Brainstem Response during Postnatal Development in Rats. Neural plasticity 13 28097024
2011 Membrane thickness sensitivity of prestin orthologs: the evolution of a piezoelectric protein. Biophysical journal 13 21641306
2009 Voltage and frequency dependence of prestin-associated charge transfer. Journal of theoretical biology 13 19490917
2005 Prestin-dependent and prestin-independent motility of guinea pig outer hair cells. Hearing research 13 16000248

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