Prestin and high frequency hearing in mammals.
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ABSTRACT:
SUBMITTER: Rossiter SJ
PROVIDER: S-EPMC3104589 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Among the vertebrate lineages with different hearing frequency ranges, humans lie between the low-frequency hearing (1 kHz) of fish and amphibians and the high-frequency hearing (100 kHz) of bats and dolphins. Little is known about the mechanism underlying such a striking difference in the limits of hearing frequency. Prestin, responsible for cochlear amplification and frequency selectivity in mammals, seems to be the only candidate to date. Mammalian prestin is densely expressed in the lateral plasma membrane of the outer hair cells (OHCs) and functions as a voltage-dependent motor protein. To explore the molecular basis for the contribution of prestin in hearing frequency detection, we collected audiogram data from humans, dogs, gerbils, bats, and dolphins because their average hearing frequency rises in steps. We generated stable cell lines transfected with human, dog, gerbil, bat, and dolphin prestins (hPres, dPres, gPres, bPres, and nPres, respectively). The non-linear capacitance (NLC) of different prestins was measured using a whole-cell patch clamp. We found that the Q max/C lin of bPres and nPres was significantly higher than that of humans. The V 1 / 2 of hPres was more hyperpolarized than that of nPres. The z values of hPres and bPres were higher than that of nPres. We further analyzed the relationship between the high-frequency hearing limit (F max) and the functional parameters (V 1 / 2, z, and Q max/C lin) of NLC among five prestins. Interestingly, no significant correlation was found between the functional parameters and F max. Additionally, a comparative study showed that the amino acid sequences and tertiary structures of five prestins were quite similar. There might be a common fundamental mechanism driving the function of prestins. These findings call for a reconsideration of the leading role of prestin in hearing frequency perception. Other intriguing kinetics underlying the hearing frequency response of auditory organs might exist.
| S-EPMC8144510 | biostudies-literature
Project description:High-frequency hearing is particularly important for echolocating bats and toothed whales. Previously, studies of the hearing-related genes Prestin, KCNQ4, and TMC1 documented that adaptive evolution of high-frequency hearing has taken place in echolocating bats and toothed whales. In this study, we present two additional candidate hearing-related genes, Shh and SK2, that may also have contributed to the evolution of echolocation in mammals. Shh is a member of the vertebrate Hedgehog gene family and is required in the specification of the mammalian cochlea. SK2 is expressed in both inner and outer hair cells, and it plays an important role in the auditory system. The coding region sequences of Shh and SK2 were obtained from a wide range of mammals with and without echolocating ability. The topologies of phylogenetic trees constructed using Shh and SK2 were different; however, multiple molecular evolutionary analyses showed that those two genes experienced different selective pressures in echolocating bats and toothed whales compared to nonecholocating mammals. In addition, several nominally significant positively selected sites were detected in the nonfunctional domain of the SK2 gene, indicating that different selective pressures were acting on different parts of the SK2 gene. This study has expanded our knowledge of the adaptive evolution of high-frequency hearing in echolocating mammals.
| S-EPMC8049434 | biostudies-literature
Project description:The remarkable high-frequency sensitivity and selectivity of the mammalian auditory system has been attributed to the evolution of mechanical amplification, in which sound waves are amplified by outer hair cells in the cochlea. This process is driven by the recently discovered protein prestin, encoded by the gene Prestin. Echolocating bats use ultrasound for orientation and hunting and possess the highest frequency hearing of all mammals. To test for the involvement of Prestin in the evolution of bat echolocation, we sequenced the coding region in echolocating and nonecholocating species. The resulting putative gene tree showed strong support for a monophyletic assemblage of echolocating species, conflicting with the species phylogeny in which echolocators are paraphyletic. We reject the possibilities that this conflict arises from either gene duplication and loss or relaxed selection in nonecholocating fruit bats. Instead, we hypothesize that the putative gene tree reflects convergence at stretches of functional importance. Convergence is supported by the recovery of the species tree from alignments of hydrophobic transmembrane domains, and the putative gene tree from the intra- and extracellular domains. We also found evidence that Prestin has undergone Darwinian selection associated with the evolution of specialized constant-frequency echolocation, which is characterized by sharp auditory tuning. Our study of a hearing gene in bats strongly implicates Prestin in the evolution of echolocation, and suggests independent evolution of high-frequency hearing in bats. These results highlight the potential problems of extracting phylogenetic signals from functional genes that may be prone to convergence.
| S-EPMC2544561 | biostudies-literature
Project description:Some hummingbirds produce unique high-frequency vocalizations. It remains unknown whether these hummingbirds can hear these sounds, which are produced at frequencies beyond the range at which most birds can hear. Here, we show behavioral and neural evidence of high-frequency hearing in a hummingbird, the Ecuadorian Hillstar (Oreotrochilus chimborazo). In the field, hummingbirds responded to playback of high-frequency song with changes in body posture and approaching behavior. We assessed neural activation by inducing ZENK expression in the brain auditory areas in response to the high-frequency song. We found higher ZENK expression in the auditory regions of hummingbirds exposed to the high-frequency song compared to controls, while no difference was observed in the hippocampus between groups. The behavioral and neural responses show that this hummingbird can hear sounds at high frequencies. This is the first evidence of the use of high-frequency vocalizations and high-frequency hearing in conspecific communication in a bird.
| S-EPMC7439503 | biostudies-literature
Project description:Cochlear outer hair cells change their length in response to variations in membrane potential. This capability, called electromotility, is believed to enable the sensitivity and frequency selectivity of the mammalian cochlea. Prestin is a transmembrane protein required for electromotility. Homozygous prestin knockout mice are profoundly hearing impaired. In humans, a single nucleotide change in SLC26A5, encoding prestin, has been reported in association with hearing loss. This DNA sequence variation, IVS2-2A>G, occurs in the exon 3 splice acceptor site and is expected to abolish splicing of exon 3.To further explore the relationship between hearing loss and the IVS2-2A>G transition, and assess allele frequency, genomic DNA from hearing impaired and control subjects was analyzed by DNA sequencing. SLC26A5 genomic DNA sequences from human, chimp, rat, mouse, zebrafish and fruit fly were aligned and compared for evolutionary conservation of the exon 3 splice acceptor site. Alternative splice acceptor sites within intron 2 of human SLC26A5 were sought using a splice site prediction program from the Berkeley Drosophila Genome Project.The IVS2-2A>G variant was found in a heterozygous state in 4 of 74 hearing impaired subjects of Hispanic, Caucasian or uncertain ethnicity and 4 of 150 Hispanic or Caucasian controls (p = 0.45). The IVS2-2A>G variant was not found in 106 subjects of Asian or African American descent. No homozygous subjects were identified (n = 330). Sequence alignment of SLC26A5 orthologs demonstrated that the A nucleotide at position IVS2-2 is invariant among several eukaryotic species. Sequence analysis also revealed five potential alternative splice acceptor sites in intron 2 of human SLC26A5.These data suggest that the IVS2-2A>G variant may not occur more frequently in hearing impaired subjects than in controls. The identification of five potential alternative splice acceptor sites in intron 2 of human SLC26A5 suggests a potential mechanism by which expression of prestin might be maintained in cells carrying the SLC26A5 IVS2-2A>G DNA sequence variation. Additional studies are needed to evaluate the effect of the IVS2-2A>G transition on splicing of SLC26A5 transcripts and characterize the hearing status of individuals homozygous for the IVS2-2A>G variant.
| S-EPMC1190179 | biostudies-literature
Project description:ObjectivesRecently, it has been hypothesized that blood prestin concentration levels may reflect cochlear damage and thus serve as an easily measurable, early sensorineural hearing loss (HL) biomarker. This is a scoping review aiming to identify and critically appraise current evidence on prestin blood levels and their temporal variation in rodents and humans with normal hearing and with sensorineural HL.DesignThis study was designed and held according to PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines. With no limitation with regards to study type, animal and human studies focusing on prestin blood levels in normal hearing and in sensorineural HL were sought in major databases such as Medline, Central Scopus, PROSPERO, and Clinicaltrials.gov. Results were then hand-searched. A data charting form was developed including the parameters of interest.ResultsSeven studies focusing on measuring prestin blood levels by means of ELISA in rodents and human subjects with normal hearing and noise-induced, drug-induced, or idiopathic sudden HL were found eligible and were included in the analysis. According to these proof-of-concept studies, prestin can be detected in the circulation of subjects with no HL; however, normal ranges remain unclear. After cochlear damage, blood prestin levels seem to initially rise and then return to near or below baseline. The degree of their change relates with subjects' degree of HL, damaged cochlear region and recovery. Prestin blood levels and their temporal variation seem to correlate with cochlear damage; however, methodological weaknesses, such as small sample size, lack of detailed phenotyping, insufficient exclusion of confounding factors, and short follow-up, do not allow for robust conclusions.ConclusionsCurrent findings support the value of studying blood prestin levels in normal hearing and HL and highlight a need for larger-scale longitudinal research.
| S-EPMC8378539 | biostudies-literature
Project description:The mammalian protein prestin is expressed in the lateral membrane wall of the cochlear hair outer cells and is responsible for the electromotile response of the basolateral membrane, following hyperpolarisation or depolarisation of the cells. Its impairment marks the onset of severe diseases, like non-syndromic deafness. Several studies have pointed out possible key roles of residues located in the Transmembrane Domain (TMD) that differentiate mammalian prestins as incomplete transporters from the other proteins belonging to the same solute-carrier (SLC) superfamily, which are classified as complete transporters. Here, we exploit the homology of a prototypical incomplete transporter (rat prestin, rPres) and a complete transporter (zebrafish prestin, zPres) with target structures in the outward open and inward open conformations. The resulting models are then embedded in a model membrane and investigated via a rigorous molecular dynamics simulation protocol. The resulting trajectories are analyzed to obtain quantitative descriptors of the equilibration phase and to assess a structural comparison between proteins in different states, and between different proteins in the same state. Our study clearly identifies a network of key residues at the interface between the gate and the core domains of prestin that might be responsible for the conformational change observed in complete transporters and hindered in incomplete transporters. In addition, we study the pathway of Cl- ions in the presence of an applied electric field towards their putative binding site in the gate domain. Based on our simulations, we propose a tilt and shift mechanism of the helices surrounding the ion binding cavity as the working principle of the reported conformational changes in complete transporters.
| S-EPMC8347359 | biostudies-literature
Project description:Membrane protein prestin is a critical component of the motor complex that generates forces and dimensional changes in cells in response to changes in the cell membrane potential. In its native cochlear outer hair cell, prestin is crucial to the amplification and frequency selectivity of the mammalian ear up to frequencies of tens of kHz. Other cells transfected with prestin acquire voltage-dependent properties similar to those of the native cell. The protein performance is critically dependent on chloride ions, and intrinsic protein charges also play a role. We propose an electro-diffusion model to reveal the frequency and voltage dependence of electric charge transfer by prestin. The movement of the combined charge (i.e., anion and protein charges) across the membrane is described with a Fokker-Planck equation coupled to a kinetic equation that describes the binding of chloride ions to prestin. We found a voltage- and frequency-dependent phase shift between the transferred charge and the applied electric field that determines capacitive and resistive components of the transferred charge. The phase shift monotonically decreases from zero to -90 degrees as a function of frequency. The capacitive component as a function of voltage is bell-shaped, and decreases with frequency. The resistive component is bell-shaped for both voltage and frequency. The capacitive and resistive components are similar to experimental measurements of charge transfer at high frequencies. The revealed nature of the transferred charge can help reconcile the high-frequency electrical and mechanical observations associated with prestin, and it is important for further analysis of the structure and function of this protein.
| S-EPMC2753271 | biostudies-literature
Project description:Young healthy adults can hear tones up to at least 20 kHz. However, clinical audiometry, by which hearing loss is diagnosed, is limited at high frequencies to 8 kHz. Evidence suggests there is salient information at extended high frequencies (EHFs; 8 to 20 kHz) that may influence speech intelligibility, but whether that information is used in challenging listening conditions remains unknown. Difficulty understanding speech in noisy environments is the most common concern people have about their hearing and usually the first sign of age-related hearing loss. Digits-in-noise (DIN), a widely used test of speech-in-noise perception, can be sensitized for detection of high-frequency hearing loss by low-pass filtering the broadband masking noise. Here, we used standard and EHF audiometry, self-report, and successively higher cutoff frequency filters (2 to 8 kHz) in a DIN test to investigate contributions of higher-frequency hearing to speech-in-noise perception. Three surprising results were found. First, 74 of 116 "normally hearing," mostly younger adults had some hearing loss at frequencies above 8 kHz. Early EHF hearing loss may thus be an easily measured, preventive warning to protect hearing. Second, EHF hearing loss correlated with self-reported difficulty hearing in noise. Finally, even with the broadest filtered noise (?8 kHz), DIN hearing thresholds were significantly better (P < 0.0001) than those using broadband noise. Sound energy above 8 kHz thus contributes to speech perception in noise. People with "normal hearing" frequently report difficulty hearing in challenging environments. Our results suggest that one contribution to this difficulty is EHF hearing loss.
| S-EPMC6876232 | biostudies-literature
Project description:The hair cells of the vertebrate inner ear posses active mechanical processes to amplify their inputs. The stereocilia bundle of various vertebrate animals can produce active movements. Though standard stereocilia-based mechanisms to promote amplification persist in mammals, an additional radically different mechanism evolved: the so-called somatic electromotility which refers to the elongation/contraction of the outer hair cells' (OHC) cylindrical cell body in response to membrane voltage changes. Somatic electromotility in OHCs, as the basis for cochlear amplification, is a mammalian novelty and it is largely dependent upon the properties of the unique motor protein prestin. We review recent literature which has demonstrated that although the gene encoding prestin is present in all vertebrate species, mammalian prestin has been under positive selective pressure to acquire motor properties, probably rendering it fit to serve somatic motility in outer hair cells. Moreover, we discuss data which indicates that a modified α10 nicotinic cholinergic receptor subunit has co-evolved in mammals, most likely to give the auditory feedback system the capability to control somatic electromotility.
| S-EPMC2888882 | biostudies-literature