Chloride/Multiple Anion Exchanger SLC26A Family: Systemic Roles of SLC26A4 in Various Organs

Abstract

Solute carrier family 26 member 4 (SLC26A4) is a member of the SLC26A transporter family and is expressed in various tissues, including the airway epithelium, kidney, thyroid, and tumors. It transports various ions, including bicarbonate, chloride, iodine, and oxalate. As a multiple-ion transporter, SLC26A4 is involved in the maintenance of hearing function, renal function, blood pressure, and hormone and pH regulation. In this review, we have summarized the various functions of SLC26A4 in multiple tissues and organs. Moreover, the relationships between SLC26A4 and other channels, such as cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and sodium chloride cotransporter, are highlighted. Although the modulation of SLC26A4 is critical for recovery from malfunctions of various organs, development of specific inducers or agonists of SLC26A4 remains challenging. This review contributes to providing a better understanding of the role of SLC26A4 and development of therapeutic approaches for the SLC26A4-associated hearing loss and SLC26A4-related dysfunction of various organs.

Keywords: SLC26A transporters; SLC26A4; anion exchanger; bicarbonate transporters.

Figure 1

Role of SLC26A4 in airway epithelial cells. Schematic illustration of the physiological roles of SLC26A4 in airway epithelial cells. The transportation of HCO₃⁻ through SLC26A4 maintains ASL thickness, and abnormal activation of SLC26A4 induces chronic inflammation, which is inhibited by RhoA.

Figure 2

Relationship between hormonal reactions and SLC26A4 expression in the kidney. SLC26A4 is activated by aldosterone and angiotensin II in type B intercalated cells to transport Cl⁻ and HCO₃⁻. Increased activation of SLC26A4 induces high blood pressure. MR: mineralocorticoid receptor.

Figure 3

Distribution of SLC26A transporters. SLC26A transporters are distributed in the kidney cells. SLC26A1 (basal membrane) and Slc26a2 (luminal membrane) are expressed in proximal tubular cells. Slc26a7 (basal membrane) and Slc26a11 (luminal membrane) are expressed in type A intercalated cells. Slc26a11 (basal membrane) and Slc26a4 (luminal membrane) are expressed in type B intercalated cells.