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|
|Organism||Homo sapiens (Human)|
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.
Fig.1 Na+-dependent HCO3-/HCO3- exchange under low Cl- concentrations. (Peña-Münzenmayer, 2016)
Application of SLC4A9 Membrane Protein in Literature
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.
The research makes a conclusion that AE4 is functionally expressed in submandibular acinar cells and involved in the cAMP-dependent regulation of fluid secretion.
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.
This study shows that acidosis reduces AE4 expression in β-ICs and diminishes pendrin in apical recycling endosomes.
The article demonstrates that AE4 promoter appears to be a direct target of forkhead transcription factor Foxi1.
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