World Library  
Flag as Inappropriate
Email this Article


Article Id: WHEBN0002935167
Reproduction Date:

Title: Prestin  
Author: World Heritage Encyclopedia
Language: English
Subject: Hair cell, Pure tone audiometry, Cochlea, Motor protein, Organ of Corti
Publisher: World Heritage Encyclopedia


Solute carrier family 26 (anion exchanger), member 5
Symbols  ; DFNB61; PRES
External IDs GeneCards:
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Prestin is a protein that is critical to sensitive hearing in mammals. It is encoded by the SLC26A5 (solute carrier anion transporter family 26, member 5) gene.[1][2]

Prestin is the motor protein of the outer hair cells of the inner ear of the mammalian cochlea.[1] It is highly expressed in the outer hair cells, and is not expressed in the nonmotile inner hair cells. Immunolocalization shows prestin is expressed in the lateral plasma membrane of the outer hair cells, the region where electromotility occurs. The expression pattern correlates with the appearance of outer hair cell electromotility.


  • Function 1
    • Intrinsic voltage sensing 1.1
    • Anion transport 1.2
  • Discovery 2
  • Clinical significance 3
  • Blockers 4
  • References 5
  • Further reading 6


Prestin is essential in auditory processing. It is specifically expressed in the lateral membrane of outer hair cells (OHCs) of the cochlea. There is no significant difference between prestin density in high-frequency and low-frequency regions of the cochlea in fully developed mammals.[3] There is good evidence that prestin has undergone adaptive evolution in mammals [4] associated with acquisition of high frequency hearing in mammals.[5] The prestin protein shows several parallel amino acid replacements in bats and dolphins that have independently evolved ultrasonic hearing and echolocation, and it represents a rare case of convergent evolution at the sequence level.[6]

Prestin (mol. wt. 80 kDa) is a member of a distinct family of anion transporters, SLC26. Members of this family are structurally well conserved and can mediate the electroneutral exchange of chloride and carbonate across the plasma membrane of mammalian cells, two anions found to be essential for outer hair cell motility. Unlike the classical, enzymatically driven motors, this new type of motor is based on direct voltage-to-displacement conversion and acts several orders of magnitude faster than other cellular motor proteins. A targeted gene disruption strategy of prestin showed a >100-fold (or 40 dB) loss of auditory sensitivity.[7]

Prestin is a transmembrane protein that mechanically contracts and elongates leading to electromotility of outer hair cells (OHC). Electromotility is the driving force behind the somatic motor of the cochlear amplifier, which is a mammalian evolution that increases sensitivity to incoming sound wave frequencies and, thus, amplifies the signal. Previous research has suggested that this modulation takes place via an extrinsic voltage-sensor (partial anion transporter model), whereby chloride binds to the intracellular side of prestin and enters a defunct transporter, causing prestin elongation.[8] However, there is new evidence that prestin acts through an intrinsic voltage-sensor (IVS) in which intracellular chloride binds allosterically to prestin to modify shape.[9][10]

Intrinsic voltage sensing

In this model of intrinsic voltage-sensing, the movement of ions generates a nonlinear capacitance (NLC). Based upon the generated voltage and the depolarized or hyperpolarized state of the cell, prestin will transition through two distinct steps, representing the three-state model of prestin modulation.[11] Experiments show that with increasing depolarizing stimuli, prestin transitions from an elongated state to an intermediate state to a contracted state, increasing its NLC. Under hyperpolarizing conditions, NLC decreases and prestin transitions back to its elongated state. Of significance, increased membrane tension as characterized by prestin elongation decreases the chloride allosteric binding site affinity for chloride, perhaps playing a role in regulation of prestin modulation. The total estimated displacement of prestin upon modulation from elongated to contracted state is 3–4 nm2.[11] A recent study supports the IVS model showing that mutations of 12 residues that span the intracellular side of prestin’s core membrane resulted in significant decrease in NLC. Eight of the 12 residues were positively charged and are hypothesized to make up the allosteric chloride binding site of prestin.[9]

Anion transport

Although previously thought to be absent, anion transport has also been shown to be an important aspect of prestin’s ability to drive electromotility of hair cells.[9][10] This mechanism is independent of prestin’s voltage-sensing capabilities based upon mutagenesis experiments showing that different mutations lead to effects in either anion-uptake or NLC, but not both.[9] It is suggested that prestin contains an intrinsic anion-uptake mechanism based upon research showing concentration dependent [14C]formate uptake in Chinese hamster ovary (CHO) cells. These results could not be reproduced in oocytes. Therefore, prestin may require an associated cofactor for anion uptake in oocytes; however, this hypothesis is still under question. Experiments have shown that various anions can compete for prestin uptake including malate, chloride, and alkylsulfonic anions.[9][12]


Prestin was discovered by Peter Dallos's group in 2000[1] and named from the musical notation presto.

The prestin molecule was patented by its discoverers in 2003.[13]

Clinical significance

Mutations in the SLC26A5 gene have been associated with non-syndromic hearing loss.[2]


Electromotile function of mammalian prestin is blocked by the amphiphilic anion salicylate at millimolar concentrations. Application of salicylate blocks prestin function in a dose-dependent and readily reversible manner.[8]


  1. ^ a b c Zheng J, Shen W, He DZ, Long KB, Madison LD, Dallos P (Jun 2000). "Prestin is the motor protein of cochlear outer hair cells". Nature 405 (6783): 149–55.  
  2. ^ a b "Entrez Gene: SLC26A5 solute carrier family 26, member 5 (prestin)". 
  3. ^ Mahendrasingam S, Beurg M, Fettiplace R, Hackney CM (2010). "The ultrastructural distribution of prestin in outer hair cells: A post-embedding immunogold investigation of low and high frequency regions of the rat cochlea". European Journal of Neuroscience 31 (9): 1595–1605.  
  4. ^ Franchini LF, Elgoyhen AB (Dec 2006). "Adaptive evolution in mammalian proteins involved in cochlear outer hair cell electromotility". Molecular Phylogenetics and Evolution 41 (3): 622–635.  
  5. ^ Rossiter SJ, Zhang S, Liu Y (2011). "Prestin and high frequency hearing in mammals". Commun Integr Biol 4 (2): 236–9.  
  6. ^ Liu Y, Rossiter SJ, Han X, Cotton JA, Zhang S (2010). "Cetaceans on a molecular fast track to ultrasonic hearing". Curr. Biol. 20 (20): 1834–9.  
  7. ^ Liberman MC, Gao J, He DZ, Wu X, Jia S, Zuo J (September 2002). "Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier". Nature 419 (6904): 300–4.  
  8. ^ a b Oliver D, He DZ, Klöcker N, Ludwig J, Schulte U, Waldegger S, Ruppersberg JP, Dallos P, Fakler B (2001). "Intracellular Anions as the Voltage Sensor of Prestin, the Outer Hair Cell Motor Protein". Science 292 (5525): 2340–2343.  
  9. ^ a b c d e Bai JP, Surguchev A, Montoya S, Aronson PS, Santos-Sacchi J, Navaratnam D (2009). "Prestin's Anion Transport and Voltage-Sensing Capabilities Are Independent". Biophysical Journal 96 (8): 3179–3186.  
  10. ^ a b Song L, Santos-Sacchi J (2010). "Conformational State-Dependent Anion Binding in Prestin: Evidence for Allosteric Modulation". Biophysical Journal 98 (3): 371–376.  
  11. ^ a b Homma K, Dallos P (2010). "Evidence That Prestin Has at Least Two Voltage-dependent Steps". Journal of Biological Chemistry 286 (3): 2297–2307.  
  12. ^ Rybalchenko V, Santos-Sacchi J (2008). "Anion Control of Voltage Sensing by the Motor Protein Prestin in Outer Hair Cells". Biophysical Journal 95 (9): 4439–4447.  
  13. ^ US granted 6602992, Dallos P, Zheng J, Madison LD, "Mammalian prestin polynucleotides", published 2003-08-05 

Further reading

  • Markovich D (2001). "Physiological roles and regulation of mammalian sulfate transporters.". Physiol. Rev. 81 (4): 1499–533.  
  • Dallos P, Fakler B (2002). "Prestin, a new type of motor protein.". Nat. Rev. Mol. Cell Biol. 3 (2): 104–11.  
  • Dallos P, Zheng J, Cheatham MA (2006). "Prestin and the cochlear amplifier.". J. Physiol. (Lond.) 576 (Pt 1): 37–42.  
  • "Toward a complete human genome sequence.". Genome Res. 8 (11): 1097–108. 1999.  
  • Lohi H, Kujala M, Kerkelä E, Saarialho-Kere U, Kestilä M, Kere J (2001). "Mapping of five new putative anion transporter genes in human and characterization of SLC26A6, a candidate gene for pancreatic anion exchanger.". Genomics 70 (1): 102–12.  
  • Weber T, Zimmermann U, Winter H, Mack A, Köpschall I, Rohbock K, Zenner HP, Knipper M (2002). "Thyroid hormone is a critical determinant for the regulation of the cochlear motor protein prestin.". Proc. Natl. Acad. Sci. U.S.A. 99 (5): 2901–6.  
  • Liberman MC, Gao J, He DZ, Wu X, Jia S, Zuo J (2002). "Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier.". Nature 419 (6904): 300–4.  
  • Liu XZ, Ouyang XM, Xia XJ, Zheng J, Pandya A, Li F, Du LL, Welch KO, Petit C, Smith RJ, Webb BT, Yan D, Arnos KS, Corey D, Dallos P, Nance WE, Chen ZY (2004). "Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss.". Hum. Mol. Genet. 12 (10): 1155–62.  
  • Dong XX, Iwasa KH (2004). "Tension sensitivity of prestin: comparison with the membrane motor in outer hair cells.". Biophys. J. 86 (2): 1201–8.  
  • Matsuda K, Zheng J, Du GG, Klöcker N, Madison LD, Dallos P (2004). "N-linked glycosylation sites of the motor protein prestin: effects on membrane targeting and electrophysiological function.". J. Neurochem. 89 (4): 928–38.  
  • Chambard JM, Ashmore JF (2005). "Regulation of the voltage-gated potassium channel KCNQ4 in the auditory pathway.". Pflugers Arch. 450 (1): 34–44.  
  • Rajagopalan L, Patel N, Madabushi S, Goddard JA, Anjan V, Lin F, Shope C, Farrell B, Lichtarge O, Davidson AL, Brownell WE, Pereira FA (2006). "Essential helix interactions in the anion transporter domain of prestin revealed by evolutionary trace analysis.". J. Neurosci. 26 (49): 12727–34.  
  • Toth T, Deak L, Fazakas F, Zheng J, Muszbek L, Sziklai I (2007). "A new mutation in the human pres gene and its effect on prestin function.". Int. J. Mol. Med. 20 (4): 545–50.  

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.

Copyright © World Library Foundation. All rights reserved. eBooks from World eBook Library are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.