SLC26A4 Membrane Protein Introduction

Introduction of SLC26A4

Pendrin (SLC26A4), encoded by the SLC26A4 gene, is a highly hydrophobic membrane protein consisting of 780 amino acids. It is also known as Sodium-independent chloride/iodide transporter and Solute carrier family 26 member 4. SLC26A4 is a highly hydrophobic membrane protein consisting of 780 amino acids. It is thought to have 12 transmembrane domains with an intracellular amino- and carboxy-terminus, and it has three putative extracellular N-glycosylation sites. SLC26A4 contains a so-called STAS (sulfate transporter and antisigma factor antagonist) domain in its intracellular carboxyterminus.

Basic Information of SLC26A4
Protein Name Pendrin
Gene Name SLC26A4
Aliases Sodium-independent chloride/iodide transporter, Solute carrier family 26 member 4
Organism Homo sapiens (Human)
UniProt ID O43511
Transmembrane Times 12
Length (aa) 780

Function of SLC26A4 Membrane Protein

SLC26A4 is a member of the multifunctional SLC26 transporter family facilitating the passive efflux of iodide across the apical thyrocyte membrane into the follicular lumen. In the inner ear, chloride/bicarbonate exchange by SLC26A4 is crucial for acid-base homeostasis of the endolymphatic fluid. In humans, loss-of-function mutations in SLC26A4 cause the genetic disorder of pendred syndrome, associated with deafness and variably penetrant hypothyroid goiter. SLC26A4 is believed to mediate apical Cl-/HCO3- exchange in epithelial cells of the inner ear, regulating pH and Cl- concentration of endolymph, and to mediate apical Cl-/I-exchange in thyrocytes, regulating I- transfer into the colloid space. SLC26A4 is needed by the mouse to excrete a HCO3- load in conditions of mineralocorticoid excess. Subsequent studies have shown the importance of murine pendrin to the regulation of distal Cl- reabsorption and to mineralocorticoid-induced hypertension. Meanwhile, it has been suggested that the STAS domain of SLC26A4, can interact with the regulatory domain of CFTR (cystic fibrosis transmembrane conductance regulator) in some epithelial cells.

The signaling pathway of SLC26A4 (Pendrin) membrane protein. Fig.1 The signaling pathway of SLC26A4 (Pendrin) membrane protein. (Tae, 2014)

Application of SLC26A4 Membrane Protein in Literature

  1. Kuwabara M.F., et al. The extracellular loop of pendrin and prestin modulates their voltage-sensing property. J. Biol. Chem. 2018, 293(26): 9970-9980. PubMed ID: 9777056

    The results of this article demonstrate that pendrin (SLC26A4) exhibits large nonlinear capacitance and that charged residues present in one of the extracellular loops of pendrin play significant roles in setting the voltage-operating points of nonlinear capacitance.

  2. Varasteh K.M., et al. Downregulation of the Cl-/HCO3- Exchanger Pendrin in Kidneys of Mice with Cystic Fibrosis: Role in the Pathogenesis of Metabolic Alkalosis. Cellular Physiology and Biochemistry. 2018, 45(4): 1551-1565. PubMed ID: 9482189

    The authors in this article propose that patients with cystic fibrosis are prone to the development of metabolic alkalosis secondary to the inactivation of the bicarbonate secreting transporter pendrin (SLC26A4), specifically during volume depletion, which is a common occurrence in cystic fibrosis patients.

  3. Royaux I.E., et al. Pendrin, the Protein Encoded by the Pendred Syndrome Gene (PDS), Is an Apical Porter of Iodide in the Thyroid and Is Regulated by Thyroglobulin in FRTL-5 Cells. Endocrinology. 2000, 141(2): 839-845. PubMed ID: 10650967

    This article suggests that pendrin (SLC26A4) is an apical porter of iodide in the thyroid and that the expression and function of both the apical and basal iodide porters are coordinately regulated by follicular thyroglobulin.

  4. Soleimani M. The multiple roles of pendrin in the kidney. Nephrology Dialysis Transplantation. 2015, 30(8): 1257-1266. PubMed ID: 25281699

    This article summarizes recent advances in the characterization of pendrin (SLC26A4) and the multiple roles it plays in the kidney, with emphasis on its essential roles in several diverse physiological processes, including chloride homeostasis, vascular volume and blood pressure regulation, calcium excretion, and kidney stone formation.

  5. Jia C-E., et al. Pendrin, an anion exchanger on lung epithelial cells, could be a novel target for lipopolysaccharide-induced acute lung injury mice. American Journal of Translational Research. 2016, 8(2): 981-992. PubMed ID: 27158384

    This article reports that pendrin (SLC26A4) may be involved in the pathological process of LPS-induced acute lung injury. Inhibition of the pendrin function could be used to treat acute lung injury. Airway epithelial cell may be a valuable therapeutic target for discovering and developing new drugs and/or new therapeutic strategies for the treatment of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS).

SLC26A4 Preparation Options

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  1. Tae S Y., et al. (2014) Gene Methylation Associated with Differentiated Thyroid Cancer. J Korean Thyroid Assoc. 7(2): 118-128.

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