Slc26a5

Solute carrier family 26, member 5 (prestin)
Identifiers
SLC26A5 Gene
Orthologs
SpeciesHumanMouse

Prestin is a protein that in humans is encoded by the SLC26A5 (solute carrier anion transporter family 26, member 5) gene.[1][2]

Prestin is the electromotility occurs. The expression pattern correlates with the appearance of outer hair cell electromotility.

Function

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 associated with acquisition of high frequency hearing in mammals.[4] 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.[5]

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.[6]

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.[7] 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.[8][9]

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.[10] 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.[10] 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.[8]

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.[8][9] 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.[8] 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.[8][11]

Discovery

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

The prestin molecule was patented by its discoverers in 2003.[12]

Clinical significance

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

Blockers

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 (Oliver et al., Science, 2001).

References

Further reading

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 USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov 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.