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.

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

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

Based on the versatile Magic™ membrane protein production platform, Creative Biolabs can help you to obtain the best soluble and functional target protein to make your project a success. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SLC4A9 antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

As a forward-looking biotech company as well as a leading custom service provider in the field of membrane protein, Creative Biolabs has won good reputation among our worldwide customers for successfully accomplishing numerous challenging projects including generation of many functional membrane proteins. Our scientific team provides access to a comprehensive solution for membrane protein studies for our clients all over the world. Please feel free to contact us for more information.

Reference

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.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.