SLC4A9 Membrane Protein Introduction

Introduction of SLC4A9

SLC4A9 (solute carrier family 4, member 9), also known as AE4, is a Na+-independent anion exchanger (AE). It belongs to the solute carrier family 4 of Cl(-)/HCO3(-) exchangers that contain products of 11 human genes (SLC4A1-5, A6, A7-11). They are composed of Na+-independent anion exchangers (AEs) SLC4A1 (AE1), SLC4A2 (AE2), SLC4A3 (AE3), and SLC4A9 (AE4) and Na+-coupled bicarbonate transporters (NBCs). There are structural and functional similarities between all transporters of the SLC4 gene family. AE polypeptides consist of three distinct domains: a hydrophilic cytoplasmic N-terminal domain of ~400-700 amino acids, a hydrophobic transmembrane domain of ~500 amino acids, and a cytoplasmic C-terminal domain consisting of ~30-100 amino acids.

Basic Information of SLC4A9
Protein Name Anion exchange protein 4
Gene Name SLC4A9
Aliases AE4
Organism Homo sapiens (Human)
UniProt ID Q96Q91
Transmembrane Times 12
Length (aa) 983

Function of SLC4A9 Membrane Protein

SLC4A9 (AE4) is a membrane protein involved in anion exchange. It has been found to be expressed on the apical membrane of gastric mucous cells and duodenal epithelial cells in mouse, rabbit, and human. However, the function of SLC4A9 in HCO3(-) secretion and chloride absorption in gastric and duodenal epithelial cells is unclear. Early research suggests that SLC4A9 is a Na(+)-independent anion exchanger. However, a recent study reveals that it is an electroneutral monovalent cation-dependent Cl(-)/HCO3(-) exchanger that mediates Cl(-)/HCO3(-) exchange activity in the presence of K(+) as well as Cs(+), Li(+), and Rb(+). SLC4 family members have been shown to play an important role in exocrine gland fluid secretion by promoting intracellular Cl(-) accumulation. Indeed, expression of SLC4A9 is found in secretory acinar cells such as salivary gland acinar cells and involved in the regulation of intracellular Cl(-) accumulation in exchange for KHCO3 efflux. Mice lacking SLC4A9 Cl(-)/HCO3(-) exchangers reduce HCO3(-)-dependent Cl(-) uptake and thus decrease saliva secretion. These all suggest SLC4A9 appears to play an important role in fluid secretion.

Na+-dependent HCO3-/HCO3- exchange under low Cl- concentrations. Fig.1 Na+-dependent HCO3-/HCO3- exchange under low Cl- concentrations. (Peña-Münzenmayer, 2016)

Application of SLC4A9 Membrane Protein in Literature

  1. Peña-Münzenmayer G., et al. Ae4 (Slc4a9) is an electroneutral monovalent cation-dependent Cl-/HCO3- exchanger. Journal of General Physiology. 2016, 147(5):423-436. PubMed ID: 27114614

    The study identifies Slc4a9 as an electroneutral Cl(-)/nonselective cation-HCO3(-) exchanger and demonstrates AE4 promotes Cl(-) influx in exchange for K(+)(Na(+)) and HCO3(-) ions in secretory cells.

  2. Peñamünzenmayer G., et al. Ae4 (Slc4a9) anion exchangers drive Cl-uptake-dependent fluid secretion by mouse submandibular gland acinar cells. Journal of Biological Chemistry. 2015, 290(17):10677-10688. PubMed ID: 25745107

    The research makes a conclusion that AE4 is functionally expressed in submandibular acinar cells and involved in the cAMP-dependent regulation of fluid secretion.

  3. Vera-Sigüenza E., et al. A mathematical model supports a key role for Ae4 (Slc4a9) in salivary gland secretion. Bulletin of Mathematical Biology. 2018, 80(2):255-282. PubMed ID: 29209914

    In this study, a mathematical model of a salivary gland acinar cell is used to investigate the role of Ae2 (Slc4a2) and Ae4 (Slc4a9) in saliva secretion and the results show that AE4 plays an important role in saliva secretion.

  4. Purkerson J.M., et al. Insights into acidosis-induced regulation of SLC26A4 (pendrin) and SLC4A9 (AE4) transporters using three-dimensional morphometric analysis of β-intercalated cells. Am J Physiol Renal Physiol. 2014, 307(5):F601-11. PubMed ID: 24990900

    This study shows that acidosis reduces AE4 expression in β-ICs and diminishes pendrin in apical recycling endosomes.

  5. Kurth I., et al. The forkhead transcription factor Foxi1 directly activates the AE4 promoter. Biochemical Journal. 2006, 393(1):277-83. PubMed ID: 16159312

    The article demonstrates that AE4 promoter appears to be a direct target of forkhead transcription factor Foxi1.

SLC4A9 Preparation Options

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  1. Peña-Münzenmayer G, et al. (2016). Ae4 (Slc4a9) is an electroneutral monovalent cation-dependent Cl-/HCO3- exchanger. Journal of General Physiology. 147(5): 423-436.

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