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AliasesSLC26A5, DFNB61, PRES, solute carrier family 26 member 5
External IDsOMIM: 604943 MGI: 1933154 HomoloGene: 69472 GeneCards: SLC26A5
Gene location (Human)
Chromosome 7 (human)
Chr.Chromosome 7 (human)[1]
Chromosome 7 (human)
Genomic location for SLC26A5
Genomic location for SLC26A5
Band7q22.1Start103,352,730 bp[1]
End103,446,207 bp[1]
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC)Chr 7: 103.35 – 103.45 MbChr 5: 21.81 – 21.87 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

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.[5][6]

Prestin is the motor protein of the outer hair cells of the inner ear of the mammalian cochlea.[5] 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.


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.[7] There is good evidence that prestin has undergone adaptive evolution in mammals [8] associated with acquisition of high frequency hearing in mammals.[9] The prestin protein shows several parallel amino acid replacements in bats, whales, and dolphins that have independently evolved ultrasonic hearing and echolocation, and these represent rare cases of convergent evolution at the sequence level.[10][11]

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.[12]

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.[13] 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.[14][15]

Intrinsic voltage sensing[edit]

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.[16] 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.[16] 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.[14]

Anion transport[edit]

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.[14][15] 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.[14] 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.[14][17]


Prestin was discovered by Peter Dallos's group in 2000[5] and named from the musical notation presto.

The prestin molecule was patented by its discoverers in 2003.[18]

Clinical significance[edit]

Mutations in the SLC26A5 gene have been associated with non-syndromic hearing loss.[6]


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.[13]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000170615 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029015 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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. Bibcode:2000Natur.405..149Z. doi:10.1038/35012009. PMID 10821263.
  6. ^ a b "Entrez Gene: SLC26A5 solute carrier family 26, member 5 (prestin)".
  7. ^ 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. doi:10.1111/j.1460-9568.2010.07182.x. PMC 2925464. PMID 20525072.
  8. ^ 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. doi:10.1016/j.ympev.2006.05.042. PMID 16854604.
  9. ^ Rossiter SJ, Zhang S, Liu Y (2011). "Prestin and high frequency hearing in mammals". Commun Integr Biol. 4 (2): 236–9. doi:10.4161/cib.4.2.14647. PMC 3104589. PMID 21655450.
  10. ^ 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. doi:10.1016/j.cub.2010.09.008. PMID 20933423.
  11. ^ Li Y, Liu Z, Shi P, Zhang P (2010). "The hearing gene Prestin unites echolocating bats and whales". Curr. Biol. 20 (2): R55–R56. doi:10.1016/j.cub.2009.11.042. PMID 20129037.
  12. ^ 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. Bibcode:2002Natur.419..300L. doi:10.1038/nature01059. PMID 12239568.
  13. ^ 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. doi:10.1126/science.1060939. PMID 11423665.
  14. ^ 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. Bibcode:2009BpJ....96.3179B. doi:10.1016/j.bpj.2008.12.3948. PMC 2718310. PMID 19383462.
  15. ^ 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. Bibcode:2010BpJ....98Q.371S. doi:10.1016/j.bpj.2009.10.027. PMC 2814207. PMID 20141749.
  16. ^ 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. doi:10.1074/jbc.M110.185694. PMC 3023524. PMID 21071769.
  17. ^ 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. Bibcode:2008BpJ....95.4439R. doi:10.1529/biophysj.108.134197. PMC 2567960. PMID 18658219.
  18. ^ US granted 6602992, Dallos P, Zheng J, Madison LD, "Mammalian prestin polynucleotides", published 2003-08-05 

Further reading[edit]

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