SLC26A5

What is SLC26A5 Protein?

SLC26A5, better known as Prestin, is a key protein found abundantly in the side membrane of outer hair cells (OHCs) in the cochlea. This protein is pivotal for the strong electromechanical movements of the cells, linked to what’s called a voltage-dependent nonlinear capacitance (NLC), reflecting its shape changes. By altering cell length, SLC26A5 enhances sound levels, providing the vertebrate auditory system with its acute sensitivity and precise frequency selection. Unlike traditional motor proteins, Prestin operates at lightning-fast microsecond speeds. Alterations in this gene could lead to sensorineural hearing loss. Beyond the ear, SLC26A5 is also expressed in various tissues, including the adrenal glands and kidneys.

What is the Function of SLC26A5 Protein?

The SLC26A5 protein, known as Prestin, acts as a molecular motor in the cochlea’s outer hair cells, crucial for amplifying sound by altering cell length. Although it’s a partial anion transporter, it doesn’t directly let anions pass through the cell membrane. Instead, it changes shape in response to shifts in chloride ion levels inside the cell, causing these length changes essential for normal hearing. Prestin operates much faster than typical motor proteins, and mutations in its gene can potentially cause sensorineural hearing loss. Besides its auditory function, Prestin might also contribute to heart mechanics by serving as an elastic component, boosting actin-driven muscle contractions.

SLC26A5 Related Signaling Pathway

Prestin, or SLC26A5, plays a crucial role in hearing by boosting auditory sensitivity and frequency tuning through outer hair cells in the cochlea. While it’s part of the SLC26 anion transporter family, Prestin’s main job isn’t moving ions directly across membranes. Instead, it undergoes shape changes when internal chloride levels shift, altering cell length and enhancing sound amplification. Beyond hearing, SLC26A5 is linked to other pathways, such as inflammation. It might intersect with inflammation and immune response signaling, especially when triggered by TLR pathways that activate MAP kinase, NF-κB, and IRF. Thus, Prestin is integral not only to hearing but also potentially to inflammatory responses.

SLC26A5 Related Diseases

The SLC26A5 protein is linked to various hearing-related conditions. SLC26A5 is mainly linked to a type of hearing loss called Autosomal Recessive 61, and Pendred syndrome, a genetic disorder often causing thyroid problems and hearing impairment. Additionally, it has an important role in how the inner ear works and is associated with non-syndromic neurosensory deafness. Mutations in the SLC26A5 gene might also contribute to sensorineural hearing loss. These connections highlight the critical role of SLC26A5 in maintaining proper auditory functions, and disruptions in its operation can lead to hearing impairments.

Bioapplications of SLC26A5

The recombinant SLC26A5 protein plays a significant role in scientific research, industrial production, and medical studies. In basic science, it’s used to explore the structure and function of SLC26A5, shedding light on its role in outer hair cells of the cochlea and the mechanisms of sound amplification. Medically, this protein helps us understand SLC26A5-related conditions like deafness and paves the way for potential treatments. Beyond these uses, recombinant SLC26A5 protein is crucial for developing diagnostic tools, such as ELISA kits, which detect disease markers. These applications not only deepen our grasp of SLC26A5’s functions but also offer fresh avenues for diagnosing and treating related diseases.

Case Study 1: Zhongying Wang, 2021

Prestin (SLC26A5) plays a key role in how vertebrates hear, enabling acute sensitivity and specific frequency detection. Our knowledge largely comes from techniques like site-directed mutagenesis, comparing prestin’s sequence to similar proteins. In amphibians, research on prestin has been limited, with the American bullfrog, Rana catesbeiana, having its SLC26A5 gene recently sequenced, mapped, and cloned using RNA-Seq. We examined prestin’s nonlinear capacitance (NLC) in both the bullfrog’s ear cells and HEK293T cells engineered to express this gene. The engineered cells mirrored the bullfrog’s ear cell characteristics. When compared, chick and zebrafish prestin lacked NLC, and a primitive frog species showed functional differences from Rana.

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  Fig1. Non-linear capacitance obtained from the rana prestin transfected cells.
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  Fig2. Non-linear capacitance obtained from the HEK293T cells expressing rana prestin.

Case Study 2: Satoe Takahashi, 2024

Mammalian SLC26 proteins are membrane-based anion transporters linked to hereditary diseases. Structural studies show that many SLC26 members share a similar homodimeric structure, prompting the question of how they perform varied functions. This study focused on SLC26A4, SLC26A5, and SLC26A9, revealing that a basic residue at the anion binding site is key for SLC26A4’s anion antiport and SLC26A5’s motor function. Changes to a nonpolar residue are essential for SLC26A9’s fast uncoupled anion transport. Polar residues found in the cytosolic areas are important for SLC26A4’s function, but not for SLC26A5 and SLC26A9. Also, the hydrophobic interactions between the last transmembrane helices play an essential role in SLC26A4 and SLC26A5.

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  Fig3. The membrane targeting efficiencies of the SLC26 constructs.
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  Fig4. NLC recorded in HEK293T cells expressing naked mole-rat SLC26A5.

SLC26A5 has several biochemical functions, for example, anion:anion antiporter activity,bicarbonate transmembrane transporter activity,chloride channel activity. Some of the functions are cooperated with other proteins, some of the functions could acted by SLC26A5 itself. We selected most functions SLC26A5 had, and list some proteins which have the same functions with SLC26A5. You can find most of the proteins on our site.

Function	Related Protein
oxalate transmembrane transporter activity	SLC26A7,SLC26A3.2,SLC26A1,SLC26A3.1,SLC26A9,SLC26A11,SLC26A2,SLC26A3,SLC26A4,SLC26A6L
spectrin binding	ADD1,EPB41,KIF3A,GNB1,GBP1,DCTN2,UNC13A,CAMSAP1L1,MYO7A,CAMSAP1
transcription factor binding	CAMTA2,NIF3L1,ETS1,UBE2I,TMEM173,LMO4,NR0B2,KCNA3,SP1,HEYL
anion:anion antiporter activity	SLC26A2,SLC26A4,SLC26A11,SLC26A3.1,Slc4a2,SLC26A3.2,SLC4A2B,SLC26A7,SLC4A8,SLC26A9
bicarbonate transmembrane transporter activity	SLC4A1,SLC26A11,CFTR,SLC26A2,SLC26A9,SLC4A11,SLC26A3.2,SLC26A1,SLC26A4,SLC26A6
secondary active sulfate transmembrane transporter activity	SLC26A3,SLC26A1,SLC26A4,SLC26A9,SLC26A11,SLC26A7,SLC26A6L,SLC26A6,SLC26A2,SLC26A3.1
sulfate transmembrane transporter activity	SLC26A3.1,SLC26A3.2,SLC26A4,SLC26A3,SLC26A1,SLC26A6,SLC26A6L,SLC26A11,SLC26A2,SLC26A7
chloride channel activity	GABRG2,GABRA6,SLC1A4,GABRD,ANO2,CLIC3,SLC26A3,GRAP2,BEST1,GABRR3
protein homodimerization activity	ACTN3,PRPS1,XDH,RPL7,GDF6,TMEM192,GALE,CD247,GSTM2,TRIM37

SLC26A5 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with SLC26A5 here. Most of them are supplied by our site. Hope this information will be useful for your research of SLC26A5.