Affinage

SLC26A5

Prestin · UniProt P58743

Length
744 aa
Mass
81.3 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Prestin (SLC26A5) is the voltage-sensitive motor protein of cochlear outer hair cells that converts membrane voltage changes into mechanical force, powering the cochlear amplifier essential for mammalian hearing sensitivity. Heterologous expression confers nonlinear capacitance (NLC) and voltage-driven cell length changes (PMID:10821263), while targeted deletion in mice abolishes electromotility and causes 40–60 dB hearing loss without affecting mechanoelectrical transduction (PMID:12239568). Cryo-EM structures reveal a dimeric 7+7 inverted-repeat transmembrane architecture with a central anion-binding site where intracellular chloride acts as a voltage sensor; voltage-driven rigid-body rearrangements between core and gate domains alter the protein's cross-sectional area and deform the surrounding membrane, while salicylate competitively occupies the same site to lock prestin in a non-productive expanded state (PMID:34390643, PMID:34695838, PMID:36266333). Prestin function is further modulated by calmodulin/Ca²⁺ binding to a C-terminal intrinsically disordered region (shifting the operating voltage) (PMID:24453323), N-glycosylation at N163/N166 (regulating oligomerization and cholesterol-dependent trafficking) (PMID:15140192, PMID:19898896), PKG phosphorylation (PMID:15649974), thyroid hormone transcriptional control (PMID:11867734), and physical interaction with CFTR (PMID:20138822).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 2000 High

    The molecular identity of the outer hair cell motor had been unknown; heterologous expression of prestin in kidney cells conferred voltage-driven shape changes and NLC, establishing it as a direct voltage-to-force transducer.

    Evidence HEK cell expression with electrophysiology and motility assay

    PMID:10821263

    Open questions at the time
    • Mechanism of voltage sensing undefined
    • Oligomeric state unknown
    • Structure undetermined
  2. 2001 Medium

    The membrane topology of prestin was uncertain; epitope mapping showed both N- and C-termini are cytoplasmic, constraining transmembrane domain models.

    Evidence Immunofluorescence with/without permeabilization on epitope-tagged constructs

    PMID:11435925

    Open questions at the time
    • Number of TM segments not directly resolved
    • Single-method topology study
  3. 2002 High

    Whether prestin was essential in vivo for hearing was untested; prestin-knockout mice lost 40–60 dB cochlear sensitivity while retaining mechanoelectrical transduction, proving prestin is the cochlear amplifier motor.

    Evidence Prestin KO mouse with in vitro electromotility and in vivo auditory physiology

    PMID:12239568

    Open questions at the time
    • Cochlear amplifier mechanism at cycle-by-cycle frequencies not demonstrated
    • Contribution of somatic vs. hair-bundle motility unresolved
  4. 2002 Medium

    The nature of prestin's voltage sensor was unknown; evidence converged that cytoplasmic anions (Cl⁻, HCO₃⁻) serve as extrinsic voltage sensors rather than intrinsic charged residues, distinguishing prestin from classic voltage-gated channels.

    Evidence Synthesis of electrophysiological data showing anion dependence of NLC

    PMID:11836512

    Open questions at the time
    • Anion-binding site not identified
    • Whether intrinsic charges also contribute was unresolved
  5. 2002 High

    Transcriptional regulation of prestin was unknown; thyroid hormone was shown to control prestin expression via a TRE in the first intron and to govern its redistribution to the lateral OHC membrane during cochlear maturation.

    Evidence Reporter transactivation, genomic TRE identification, hypothyroid rat model with immunohistochemistry

    PMID:11867734

    Open questions at the time
    • Other transcription factors controlling prestin expression not identified
    • Postnatal developmental program not fully mapped
  6. 2004 High

    Post-translational modification of prestin was uncharacterized; N-glycosylation at N163/N166 was shown to shift voltage dependence of NLC without being required for membrane targeting, revealing a modulatory role.

    Evidence Site-directed mutagenesis, tunicamycin/glycopeptidase-F treatment, NLC electrophysiology

    PMID:15140192

    Open questions at the time
    • Role of glycosylation in oligomerization was not yet tested
    • In vivo significance unknown
  7. 2005 High

    Prestin's oligomeric state and the roles of its cytoplasmic domains were undefined; FRET demonstrated homomultimerization via the N-terminus, while truncation of either terminus abolished voltage sensing, indicating both termini are essential for function.

    Evidence FRET, truncation mutagenesis, NLC electrophysiology

    PMID:16113116

    Open questions at the time
    • Stoichiometry not determined by FRET alone
    • Structural basis of terminal contributions unknown
  8. 2005 Medium

    Signaling pathways modulating prestin were largely unknown; PKG phosphorylation sites were identified that modulate NLC, with cGMP having a greater effect than cAMP.

    Evidence Phosphorylation-site mutagenesis, cGMP/cAMP analog application, NLC recording

    PMID:15649974

    Open questions at the time
    • In vivo relevance of PKG regulation untested
    • Kinase/phosphatase identities not confirmed endogenously
  9. 2006 High

    The precise oligomeric assembly of prestin was debated; multiple orthogonal biochemical methods established prestin as a stable tetramer built on disulfide-bonded dimers.

    Evidence LDS-PAGE, PFO-PAGE, yeast two-hybrid, cross-linking, affinity purification

    PMID:16682411

    Open questions at the time
    • Whether dimer or tetramer is the minimal functional unit was unclear
    • No atomic structure available
  10. 2007 High

    The evolutionary relationship between electromotility and anion transport was unknown; non-mammalian prestin orthologs were shown to function as electrogenic anion antiporters, linking the motor mechanism to an ancestral transport cycle.

    Evidence Patch-clamp transport current recording in cells expressing chicken/zebrafish prestin

    PMID:17442754

    Open questions at the time
    • Whether mammalian prestin retains physiologically relevant transport was unresolved
    • Structural basis for loss of full transport cycle in mammals unknown
  11. 2007 Medium

    Membrane environment effects on prestin were unexplored; prestin was found in cholesterol-rich microdomains, and cholesterol depletion altered NLC, linking lipid composition to motor function.

    Evidence Sucrose density fractionation, immunocolocalization, cholesterol depletion, NLC electrophysiology

    PMID:17321873

    Open questions at the time
    • Mechanism of cholesterol effect on prestin conformation unknown
    • Single lab finding
  12. 2007 Medium

    Whether charge transfer is mechanistically necessary for electromechanical force was untested; the A100W mutation eliminated charge movement and diminished force without altering passive membrane mechanics, establishing this requirement.

    Evidence Membrane tether mechanics from prestin-transfected HEK cells, A100W mutagenesis

    PMID:17468166

    Open questions at the time
    • Structural interpretation of A100W effect unknown
    • Single lab
  13. 2009 High

    Whether mammalian prestin retains transport was contested; radioactive anion uptake confirmed transport, and mutations P328A/L326A uncoupled transport from voltage sensing, demonstrating these are separable functions.

    Evidence ¹⁴C-formate/oxalate uptake, site-directed mutagenesis, NLC electrophysiology

    PMID:19383462

    Open questions at the time
    • Physiological significance of residual transport in OHCs unknown
    • Structural basis for uncoupling not determined
  14. 2009 Medium

    The relationship between glycosylation and oligomerization was not established; N163/N166 glycosylation was shown to be required for oligomerization and cholesterol-dependent trafficking, explaining the earlier NLC-shift phenotype.

    Evidence NN163/166AA mutagenesis, FRAP, sucrose fractionation, cholesterol manipulation

    PMID:19898896

    Open questions at the time
    • Glycan structure on native OHC prestin not characterized
    • Single lab
  15. 2010 High

    Prestin's interacting partners in the OHC lateral wall were poorly defined; CFTR was shown to physically interact with prestin and to enhance charge displacement when activated, revealing a functional partnership.

    Evidence Co-immunoprecipitation, immunofluorescence, electrophysiology in prestin-KO controls

    PMID:20138822

    Open questions at the time
    • Molecular interface between prestin and CFTR unmapped
    • In vivo hearing consequence of disrupting this interaction untested
  16. 2010 High

    The structure of prestin's cytoplasmic STAS domain was unknown; crystal structure at 1.57 Å revealed domain architecture and mapped disease mutations to misfolding or interaction-surface defects.

    Evidence X-ray crystallography and NMR with functional mutagenesis

    PMID:20471983

    Open questions at the time
    • Full-length prestin structure not yet available
    • STAS–TM domain interface not resolved
  17. 2013 Medium

    Discrepancies between NLC and electromotility voltage dependence were unexplained; simultaneous recording showed chloride drives slow state transitions that gate voltage-enabled motors, explained by a multi-state kinetic model.

    Evidence Simultaneous NLC and electromotility under voltage clamp, kinetic modeling

    PMID:23431177

    Open questions at the time
    • Structural correlates of intermediate transitions unknown
    • Model not validated by structural data
  18. 2014 High

    The structural basis of anion binding in the transmembrane core was unknown; homology modeling with cysteine accessibility scanning revealed a 7+7 inverted repeat architecture with a central anion-binding cavity controlling electromotility.

    Evidence Homology modeling, MD simulation, SCAM, mutagenesis

    PMID:24710176

    Open questions at the time
    • Experimental high-resolution structure still lacking
    • Dynamic conformational changes during motor cycle unresolved
  19. 2014 High

    How prestin's operating voltage is tuned by intracellular signals was unclear; calmodulin was found to bind a C-terminal IDR in a Ca²⁺-dependent manner and shift the voltage operating point, establishing a Ca²⁺-mediated regulatory mechanism.

    Evidence CaM-binding assays, patch-clamp of OHCs and heterologous cells with Ca²⁺/CaM manipulation

    PMID:24453323

    Open questions at the time
    • CaM–prestin binding interface not structurally resolved
    • In vivo relevance for cochlear amplification gain not tested
  20. 2018 Medium

    Whether charged residues outside the TM core contribute to voltage sensing was untested; extracellular loop charged residues were shown to set the voltage operating point, and pendrin also exhibited NLC, indicating voltage sensing is a broader SLC26 property.

    Evidence Site-directed mutagenesis of extracellular loop, NLC electrophysiology

    PMID:29777056

    Open questions at the time
    • Structural mechanism of extracellular charge influence not determined
    • Single lab
  21. 2021 High

    The atomic mechanism of voltage-driven area change was unknown; cryo-EM structures of human and dolphin prestin in chloride-bound (contracted) and salicylate-bound (expanded) states revealed how anion-dependent conformational changes alter TM cross-sectional area and deform the membrane, defining prestin's motor mechanism at atomic resolution.

    Evidence Cryo-EM in multiple anion-bound states, MD simulation, mutagenesis, electrophysiology; two independent groups

    PMID:34390643 PMID:34695838

    Open questions at the time
    • Cycle speed at auditory frequencies not structurally captured
    • Force output per conformational transition not directly measured
  22. 2021 Medium

    Prestin's role was thought to be ear-specific; expression in cardiac myocytes and contractility defects in prestin-KO mice demonstrated a broader motor function beyond the inner ear.

    Evidence Prestin-KO mouse cardiac measurements, NLC in cardiomyocytes, immunofluorescence

    PMID:33951436

    Open questions at the time
    • Single lab, novel finding awaiting independent replication
    • Mechanism of force amplification in cardiomyocytes undefined
  23. 2022 High

    Whether chloride binding is absolutely required for voltage sensing was debated; gerbil prestin cryo-EM with chloride-site mutations showed retained NLC without salicylate sensitivity, challenging the pure extrinsic voltage sensor model and implicating intrinsic charged residues.

    Evidence Cryo-EM at 3.6 Å, chloride-binding site mutagenesis, NLC electrophysiology

    PMID:35022426

    Open questions at the time
    • Relative contributions of intrinsic vs. extrinsic voltage sensing not quantitatively partitioned
    • Functional consequences in vivo not tested
  24. 2022 High

    The role of the dimeric interface in the motor cycle was unclear; cryo-EM with three ligands showed rigid-body core–gate domain movement, and dimer-interface mutations severely diminished NLC, establishing that gate domain stabilization by dimerization is required for effective core domain movement.

    Evidence Cryo-EM in three ligand states, dimer-interface mutagenesis, NLC electrophysiology

    PMID:36266333

    Open questions at the time
    • Whether tetramer provides additional functional advantage over dimer unknown
    • Allosteric coupling between protomers not resolved
  25. 2022 Medium

    How dense prestin arrays generate macroscopic OHC shape change was not mechanistically explained; MD simulations showed prestin dimers cause anisotropic membrane deformation and self-organize into preferred orientational arrays, with constructive alignment maximizing membrane reshaping.

    Evidence Coarse-grained MD simulation at OHC-relevant protein densities

    PMID:36371434

    Open questions at the time
    • Simulation predictions not experimentally validated
    • Effect of prestin–lipid interactions on OHC mechanics untested in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions remain: how prestin generates force at cycle-by-cycle auditory frequencies (up to ~70 kHz), the quantitative partitioning of intrinsic versus extrinsic voltage sensing, the structural basis of CaM-mediated voltage tuning, and whether prestin's cardiac role is physiologically significant.
  • No time-resolved structural data at auditory frequencies
  • CaM–prestin complex structure not solved
  • Cardiac function awaits independent replication

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 1
Localization
GO:0005886 plasma membrane 5
Pathway
R-HSA-382551 Transport of small molecules 3
Partners
CALMODULINCFTRGLUT5
Complex memberships
prestin homotetramerprestin–CFTR complex

Evidence

Reading pass · 31 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 human kidney cells confers voltage-induced shape changes and nonlinear capacitance, demonstrating it is a direct voltage-to-force converter. Heterologous expression in HEK cells, electrophysiology (nonlinear capacitance), 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 physiology (CAP thresholds), heterozygote dose–response Nature High 12239568
2001 Both the N- and C-termini of prestin are cytoplasmic, as determined by epitope localization using immunofluorescence under permeabilizing and non-permeabilizing conditions. Epitope-tagged constructs, immunofluorescence with/without permeabilization Neuroreport Medium 11435925
2002 Prestin uses cytoplasmic anions (chloride or bicarbonate) as extrinsic voltage sensors to drive electromotility; it functions as a direct voltage-to-force converter without enzymatic activity. Review synthesizing electrophysiological and expression data Nature Reviews Molecular Cell Biology Medium 11836512
2002 Thyroid hormone (T3) transcriptionally regulates prestin expression via a thyroid hormone response element (TRE) in the first intron; hypothyroidism strongly reduces prestin mRNA/protein and disrupts its normal redistribution to the lateral OHC membrane. Genomic sequence analysis identifying TRE, reporter transactivation assays, in vivo hypothyroid rat model with immunohistochemistry and Western blot PNAS High 11867734
2005 Prestin is a 10-transmembrane domain protein whose N-terminus mediates homomultimerization (homo-oligomerization), demonstrated by FRET; truncation of either intracellular terminus abolishes or modifies voltage sensing despite normal membrane targeting. FRET between fluorescently tagged prestin constructs, truncation mutagenesis, electrophysiology (NLC) Biophysical Journal High 16113116
2006 Prestin exists as a stable tetramer (higher-order oligomer built on disulfide-bonded dimers) in native OHCs and heterologous expression systems, demonstrated by LDS-PAGE, PFO-PAGE, yeast two-hybrid, chemical cross-linking, and affinity purification. LDS-PAGE, PFO-PAGE, membrane-based yeast two-hybrid, chemical cross-linking, affinity purification Journal of Biological Chemistry High 16682411
2007 Non-mammalian prestin orthologs (chicken, zebrafish) function as electrogenic divalent/monovalent anion antiporters (sulfate or oxalate exchanged for chloride, 1:1), a transport activity blocked by salicylate, linking the electromotility mechanism to an anion transport cycle. Patch-clamp recordings of transport currents in heterologous cells expressing chicken/zebrafish prestin, reversal potential analysis, pharmacology PNAS High 17442754
2004 Prestin is N-glycosylated at residues N163 and N166; N-linked glycosylation is not required for plasma membrane targeting but deglycosylated prestin shows altered voltage dependence of nonlinear capacitance (shift of Vpkcm toward depolarization). Site-directed mutagenesis of N-glycosylation sites, tunicamycin/glycopeptidase-F treatment, electrophysiology (NLC), Western blot Journal of Neurochemistry High 15140192
2005 cGMP (via PKG phosphorylation sites on prestin) significantly modulates prestin nonlinear capacitance more than cAMP; specific serine/threonine residues are phosphorylation sites with potential interactions between two PKG target sites; one site may influence membrane targeting. Mutagenesis of phosphorylation sites (S→A, S→D), cGMP/cAMP analog application, NLC recording in transfected cells Journal of Physiology Medium 15649974
2009 Prestin can transport anions (formate, oxalate) in mammalian cells; two residues (P328A, L326A) uncouple transport from voltage sensing (preserving NLC while abolishing transport); 12 of 22 charged transmembrane residues contribute to unitary charge movement (voltage sensing). Radioactive anion uptake assay ([14C]formate, [14C]oxalate), site-directed mutagenesis, NLC electrophysiology Biophysical Journal High 19383462
2010 Prestin physically interacts with CFTR in OHC lateral membranes; prestin directs CFTR localization to the lateral membrane; cAMP-activated CFTR enhances prestin voltage-dependent charge displacement, while prestin does not affect CFTR chloride conductance. In situ hybridization, immunofluorescence, co-immunoprecipitation, electrophysiology Biochimica et Biophysica Acta High 20138822
2010 Crystal structure (1.57 Å) of the cytosolic STAS domain of prestin reveals it starts immediately after the last TM segment; the STAS N-terminal region lies beneath the lipid bilayer and is involved in functionally important intra- and intermolecular interactions; disease mutations map to misfolding or interaction-surface alterations. X-ray crystallography (1.57 Å), multidimensional NMR, functional mutagenesis analysis Journal of Molecular Biology High 20471983
2011 Rat prestin mediates electrogenic SCN− transport (uncoupled, not stoichiometrically linked to other anions), demonstrating that mammalian prestin retains anion transport capability shared with non-mammalian SLC26 family members. Patch-clamp recording of SCN− currents in prestin-expressing mammalian cells, concentration-dependence of reversal potential, comparison with zebrafish prestin and SLC26A7 Journal of Physiology Medium 22063625
2014 Calmodulin (CaM) binds directly to an intrinsically disordered region (IDR) in prestin's C-terminal domain in a calcium-obligate manner, shifting the operating voltage to more hyperpolarized potentials; this CaM-binding mechanism is conserved across SLC26 paralogs. Bioinformatics (IDR prediction, CaM-binding site prediction), biochemical CaM-binding assays, patch-clamp of OHCs and heterologous cells with Ca2+/CaM manipulation Journal of Neuroscience High 24453323
2014 Structural model of prestin's transmembrane core derived by homology modelling, MD simulation, and cysteine accessibility scanning reveals a 7+7 inverted repeat architecture with a central cavity as the anion-binding/substrate site midway in the permeation pathway; anion binding to this site controls electromotile activity. Homology modelling, MD simulation, cysteine accessibility scanning (SCAM), mutational analysis Nature Communications High 24710176
2007 Prestin localizes to cholesterol-rich membrane microdomains (lipid rafts) in heterologous cells; cholesterol depletion alters prestin localization and NLC, linking membrane lipid composition to prestin function. Immunocolocalization with microdomain markers, sucrose density fractionation, cholesterol depletion, NLC electrophysiology Otolaryngology–Head and Neck Surgery Medium 17321873
2009 N-glycosylation of prestin at N163/N166 is required for oligomerization and cholesterol-dependent membrane trafficking; non-glycosylated prestin (NN163/166AA) is enriched as monomers and shows increased membrane mobility; glycosylation-independent oligomerization is sufficient for NLC in basal conditions but not under elevated cholesterol. Mutagenesis (NN163/166AA), FRAP, sucrose density fractionation, cholesterol manipulation, NLC electrophysiology Journal of the Association for Research in Otolaryngology Medium 19898896
2007 Prestin interacts with GLUT5 in OHC lateral membranes, demonstrated by FRET (FACS-FRET, acceptor photobleaching FRET, FRET-FLIM) and co-immunoprecipitation in transfected HEK293T cells. Confocal colocalization, FRET (three independent FRET methods), co-immunoprecipitation Developmental Neurobiology Medium 17443803
2018 Charged residues in the extracellular loop of prestin (and pendrin) set the voltage-operating point of nonlinear capacitance; pendrin also exhibits large NLC, indicating voltage sensing is not unique to prestin among SLC26 family members and works independently of anion transport. Site-directed mutagenesis of extracellular loop charged residues, NLC electrophysiology in transfected cells Journal of Biological Chemistry Medium 29777056
2021 Cryo-EM structures of human prestin bound with chloride (contracted state) or salicylate (expanded state) at a common anion-binding site reveal how conformational changes are coupled to alterations in transmembrane domain cross-sectional area and surrounding membrane; salicylate competes with chloride at this site and inhibits prestin by locking it in the expanded conformation. Cryo-EM (multiple states), computational MD simulation, functional electrophysiology, mutagenesis Cell High 34390643
2021 Cryo-EM structures of dolphin prestin in six distinct anion-dependent states reveal: (1) bound anion plus coordinating charged residues and helical dipole act as a dynamic voltage sensor; (2) salicylate competes for the anion-binding site and immobilizes prestin in a distinct inhibited conformation; (3) structural rearrangements couple voltage-sensor changes to protein-membrane interface expansions, defining a mechanism of area change distinct from SLC26 transporters. Single-particle cryo-EM (six states), anion substitution, functional electrophysiology, mutagenesis Nature High 34695838
2022 Cryo-EM structure of gerbil prestin at 3.6 Å (inward-open state) confirms a swapped dimer with 14 TM segments in 7+7 inverted repeat architecture; mutation of the chloride-binding site removes salicylate competition while retaining displacement currents (NLC), undermining the pure extrinsic voltage sensor hypothesis. Cryo-EM (3.6 Å), site-directed mutagenesis of chloride-binding site, NLC electrophysiology Nature Communications High 35022426
2022 Cryo-EM structures of thermostabilized prestin with chloride, sulfate, or salicylate show a central positively charged cavity for flexible anion binding; rigid-body movement between core and gate domains underlies NLC; mutations at the dimeric interface severely diminish NLC, indicating gate domain stabilization facilitates core domain movement. Cryo-EM (3.52–3.63 Å, three ligand states), site-directed mutagenesis of dimeric interface, NLC electrophysiology Nature Communications High 36266333
2013 Prestin's voltage-sensor charge movement (NLC) and electromotility show disparities in voltage dependence and magnitude as a function of intracellular chloride, explained by a kinetic model with fast anion-binding and voltage-driven transitions coupled by a slower intermediate transition; chloride drives slow state transitions that gate voltage-enabled motors. Simultaneous NLC and electromotility recording under voltage clamp, kinetic modeling PNAS Medium 23431177
2016 Intracellular chloride controls prestin kinetics (and thereby apparent Qmax at any given frequency) but does not change the true total sensor charge (Qmax) as measured at low frequency; prestin activity is significantly low-pass in frequency domain. Multifrequency admittance, expanded displacement current integration, OHC electromotility across frequencies under voltage clamp Biophysical Journal Medium 27276272
2011 Prestin-driven cochlear amplification is not limited by the OHC membrane time constant because resting open mechanotransducer channels depolarize the membrane and activate a voltage-dependent K+ conductance that minimizes the time constant and expands membrane filter bandwidth. Patch-clamp of OHCs across characteristic frequencies at physiological endolymph calcium, measurement of membrane time constant and receptor potential Neuron High 21689600
2021 Prestin (SLC26A5) is expressed in cardiac myocytes (mouse and human) and amplifies actin-myosin force generation; prestin-knockout mice display significant alterations in cardiac contractility, demonstrating a broader cellular motor function beyond the inner ear. Prestin-KO mouse cardiac contractility measurements, nonlinear capacitance recording in cardiomyocytes, immunofluorescence localization Cell Reports Medium 33951436
2007 Prestin A100W point mutation eliminates prestin-associated charge transfer and diminishes electromechanical force generation by the membrane without altering passive membrane mechanics, demonstrating that prestin-associated charge transfer is necessary for maximal electromechanical force. Membrane tether mechanics from prestin-transfected HEK cells, A100W site-directed mutagenesis, electromechanical force measurement Biophysical Journal Medium 17468166
2014 Chloride flux through prestin (SLC26A5) is directly measurable using a YFP-based chloride sensor fused to gerbil prestin, confirming physiological (mM-range) chloride movement mediated by prestin in HEK cells. Genetically encoded Cl− sensor (monomeric Cl-YFP) fused to prestin, fluorescence-based chloride flux assay in HEK cells PLoS One Medium 24901231
2022 MD simulations show prestin causes anisotropic membrane deformation and organizes into preferred orientational arrays at OHC-relevant densities via lipid-mediated protein–protein interactions, with constructive alignment of deformation patterns between neighboring prestin dimers reducing membrane rigidity and maximizing OHC reshaping. Coarse-grained molecular dynamics simulation (>0.5 ms aggregate), multiple prestin densities Nature Communications Medium 36371434

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 948 10821263
2002 Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier. Nature 665 12239568
2006 Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and hepatocarcinogenesis. Cancer science 226 16863502
1984 A polypeptide containing 55 amino acid residues coded by the pre-S region of hepatitis B virus deoxyribonucleic acid bears the receptor for polymerized human as well as chimpanzee albumins. Gastroenterology 219 6323244
2014 Hepatitis B virus PreS/S gene variants: pathobiology and clinical implications. Journal of hepatology 218 24801416
2002 Prestin, a new type of motor protein. Nature reviews. Molecular cell biology 211 11836512
2011 Prestin-driven cochlear amplification is not limited by the outer hair cell membrane time constant. Neuron 207 21689600
2008 Cochlear amplification, outer hair cells and prestin. Current opinion in neurobiology 200 18809494
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 144 20129037
2003 Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss. Human molecular genetics 144 12719379
2004 Cochlear function in Prestin knockout mice. The Journal of physiology 126 15319415
1987 Regulation of secretion of the hepatitis B virus major surface antigen by the preS-1 protein. Journal of virology 120 3806798
2012 Impact of hepatitis B virus (HBV) preS/S genomic variability on HBV surface antigen and HBV DNA serum levels. Hepatology (Baltimore, Md.) 117 22271491
2008 Ground glass hepatocytes contain pre-S mutants and represent preneoplastic lesions in chronic hepatitis B virus infection. Journal of gastroenterology and hepatology 116 18505413
2008 The hearing gene Prestin reunites echolocating bats. Proceedings of the National Academy of Sciences of the United States of America 96 18776049
2002 Thyroid hormone is a critical determinant for the regulation of the cochlear motor protein prestin. Proceedings of the National Academy of Sciences of the United States of America 93 11867734
1997 A preS mutation isolated from a patient with chronic hepatitis B infection leads to virus retention and misassembly. Gastroenterology 89 9394738
2005 N-terminal-mediated homomultimerization of prestin, the outer hair cell motor protein. Biophysical journal 86 16113116
2011 A hypoallergenic cat vaccine based on Fel d 1-derived peptides fused to hepatitis B PreS. The Journal of allergy and clinical immunology 82 21411130
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 80 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 68 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
1987 Immunogenicity of the gene S and Pre-S domains in hepatitis B virions and HBsAg filaments. Intervirology 66 2448264
2021 The conformational cycle of prestin underlies outer-hair cell electromotility. Nature 64 34695838
2009 Prestin's anion transport and voltage-sensing capabilities are independent. Biophysical journal 62 19383462
2014 Molecular architecture and the structural basis for anion interaction in prestin and SLC26 transporters. Nature communications 61 24710176
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
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 52 20471983
2018 The Frequency Response of Outer Hair Cell Voltage-Dependent Motility Is Limited by Kinetics of Prestin. The Journal of neuroscience : the official journal of the Society for Neuroscience 51 29899032
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 48 25917987
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
2003 Identification and characterization of polyhomeotic PREs and TREs. Developmental biology 48 14499651
2006 Prestin is expressed on the whole outer hair cell basolateral surface. Brain research 45 16709400
1987 Selective synthesis and secretion of particles composed of the hepatitis B virus middle surface protein directed by a recombinant vaccinia virus: induction of antibodies to pre-S and S epitopes. Journal of virology 45 2434666
2021 Clinical Implications of HBV PreS/S Mutations and the Effects of PreS2 Deletion on Mitochondria, Liver Fibrosis, and Cancer Development. Hepatology (Baltimore, Md.) 44 33675094
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
2005 Cochlear function in mice with only one copy of the prestin gene. The Journal of physiology 43 16166160
2013 Prestin at year 14: progress and prospect. Hearing research 42 24361298
2022 Single particle cryo-EM structure of the outer hair cell motor protein prestin. Nature communications 41 35022426
2010 Interaction between CFTR and prestin (SLC26A5). Biochimica et biophysica acta 41 20138822
1992 Characterization of the hepatitis B virus preS/S region encoded transcriptional transactivator. Virology 39 1546461
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 38 27636386
2012 Outer hair cell-specific prestin-CreERT2 knockin mouse lines. Genesis (New York, N.Y. : 2000) 36 21954035
2009 Long-term administration of salicylate enhances prestin expression in rat cochlea. International journal of audiology 34 19173110
1995 Study on the comparative immunogenicity of a recombinant DNA hepatitis B vaccine containing pre-S components of the HBV coat protein with non pre-S containing vaccines. Journal of gastroenterology and hepatology 33 7620108
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 31 16626645
1991 Peptide mapping of neutralizing and nonneutralizing epitopes of duck hepatitis B virus pre-S polypeptide. Virology 31 1704654
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
1993 Fine mapping of neutralization epitopes on duck hepatitis B virus (DHBV) pre-S protein using monoclonal antibodies and overlapping peptides. Virology 28 7685963
2015 Therapy and differential diagnosis of posterior reversible encephalopathy syndrome (PRES) during pregnancy and postpartum. Archives of gynecology and obstetrics 27 26122264
2011 Recurrent EIARF and PRES with severe renal hypouricemia by compound heterozygous SLC2A9 mutation. Pediatrics 27 21536615
2011 Anion transport by the cochlear motor protein prestin. The Journal of physiology 27 22063625
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
2022 Noise exposure levels predict blood levels of the inner ear protein prestin. Scientific reports 25 35064195
2022 Cryo-EM structures of thermostabilized prestin provide mechanistic insights underlying outer hair cell electromotility. Nature communications 25 36266333
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 25 29065096
2010 Prestin and the cholinergic receptor of hair cells: positively-selected proteins in mammals. Hearing research 25 20056140
2009 Glycosylation regulates prestin cellular activity. Journal of the Association for Research in Otolaryngology : JARO 24 19898896
2007 Evaluation of an independent prestin mouse model derived from the 129S1 strain. Audiology & neuro-otology 24 17664869
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
2008 High prevalence of hepatitis B virus pre-S mutation and its association with hepatocellular carcinoma in Qidong, China. Archives of virology 22 18726170
2016 Chloride Anions Regulate Kinetics but Not Voltage-Sensor Qmax of the Solute Carrier SLC26a5. Biophysical journal 21 27276272
2021 Hepatitis B Virus Pre-S Gene Deletions and Pre-S Deleted Proteins: Clinical and Molecular Implications in Hepatocellular Carcinoma. Viruses 20 34066744
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
2021 Prestin amplifies cardiac motor functions. Cell reports 19 33951436
2016 HEI-OC1 cells as a model for investigating prestin function. Hearing research 19 26854618
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
2014 Chloride and salicylate influence prestin-dependent specific membrane capacitance: support for the area motor model. The Journal of biological chemistry 18 24554714
2007 Expression, purification and characterisation of the C-terminal STAS domain of the SLC26 anion transporter prestin. Protein expression and purification 18 18226918
2019 Prestin kinetics and corresponding frequency dependence augment during early development of the outer hair cell within the mouse organ of Corti. Scientific reports 17 31712635
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
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 16 29067537
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
2022 HBV preS Mutations Promote Hepatocarcinogenesis by Inducing Endoplasmic Reticulum Stress and Upregulating Inflammatory Signaling. Cancers 15 35805045
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
2020 In silico functional and structural characterization of hepatitis B virus PreS/S-gene in Iranian patients infected with chronic hepatitis B virus genotype D. Heliyon 14 32695898
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
1991 Cloning, expression, isolation and characterization of the pre-S domains of hepatitis B surface antigen, devoid of the S protein. The Biochemical journal 14 2049071
1985 Detection of antibodies directed against the pre-S gene product of hepatitis B virus: relationship between anti-pre-S response and recovery. Annales de l'Institut Pasteur. Immunologie 14 4062249
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
2016 Synchronized Progression of Prestin Expression and Auditory Brainstem Response during Postnatal Development in Rats. Neural plasticity 13 28097024
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