SLC26A3 Membrane Protein Introduction

Introduction of SLC26A3

SLC26A3 is encoded by the SLC26A3 gene and is also known as Chloride anion exchanger, Down-regulated in adenoma, Protein DRA and Solute carrier family 26 member 3. It belongs to the SLC26 gene family encodes for anion transporters that transport a variety of monovalent and divalent anions. Among the 11 members identified, SLC26A3 and SLC26A6 are the two main Cl^-/HCO₃^- exchangers expressed in various epithelial tissues. Meanwhile, SLC26A3 is predicted to contain 10 transmembrane-spanning α-helices and a C-terminal domain.

Function of SLC26A3 Membrane Protein

SLC26A3 plays an important role in embryo cleavage and thus preimplantation embryo development. SLC26A3 has been demonstrated to play an important role in mediating HCO₃^- entry required for embryo cleavage, which may have implications in fertility diagnosis or prediction of pregnancy outcome. It has been demonstrated that patients carrying mutations in SLC26A3 gene suffered congenital chloride diarrhea. SLC26A3 knockout mice also exhibit subfertility, however, whether SLC26A3 is associated with other forms of defects in fertility other than male infertility remains unexplored. Knockdown of SLC26A3 has a more potent inhibiting effect on embryo cleavage compared to SLC26A6 knockdown, suggesting a more critical role of SLC26A3 in embryo cleavage. Double knockdown of SLC26A3 and SLC26A6 showed an additive effect compared to individual knockdown. SLC26A3 appears to be predominant to contribute to HCO₃^- entry required for embryo cleavage compared to SLC26A6. SLC26A3 could be a potential biomarker for predicting pregnancy failure associated with embryo development blockage.

Fig.1 Involvement of SLC26A3 in preimplantation embryo cleavage membrane protein. (Lu, 2016)

Application of SLC26A3 Membrane Protein in Literature

1. Lu Y.C., et al. Involvement of Cl^-/HCO₃^- exchanger SLC26A3 and SLC26A6 in preimplantation embryo cleavage. Scientific Reports. 2016, 6: 28402. PubMed ID: 27346053
   
   

   The results of this article show clearly that SLC26A3 plays an important role in embryo cleavage and thus preimplantation embryo development. Meanwhile, this article proposes that SLC26A3 could be a potential biomarker for predicting pregnancy failure associated with embryo development blockage.

2. Wedenoja S., et al. A missense mutation in SLC26A3 is associated with human male subfertility and impaired activation of CFTR. Scientific Reports. 2017, 7(1): 14208. PubMed ID: 29079751
   
   

   The authors of this article suggest a novel mechanism for human male infertility impaired anion transport by the coupled SLC26A3 and CFTR because SLC26A3 is a strong activator of CFTR-dependent anion transport.

3. Xiao F., et al. Slc26a3 deficiency is associated with loss of colonic HCO₃^- secretion, absence of a firm mucus layer and barrier impairment in mice. Acta Physiologica. 2013, 211(1): 161-175. PubMed ID: 4373192
   
   

   This article demonstrates that deletion of SLC26A3 results in severely reduced colonic HCO₃^- secretory rate, a loss of colonic fluid absorption, a lack of a firmly adherent mucus layer and a severely reduced colonic mucosal resistance to dextran sodium sulphate damage.

4. Lee J.H., et al. Regulation of SLC26A3 activity by NHERF4 PDZ-mediated interaction. Cell. Signal. 2012, 24(9): 1821-1830. PubMed ID: 22627094
   
   

   This article shows that the SLC26A3–NHERF4 interaction was modulated by phosphorylation; serine 329 of NHERF4-PDZ3 played a critical role in modulating binding selectivity. The findings of this article suggest that NHERF4 is a novel modulator of luminal fluidity in the intestine by adjusting SLC26A3 expression and activity through a phosphorylation-dependent mechanism.

5. Ding X., et al. SLC26A3 (DRA) prevents TNF-alpha-induced barrier dysfunction and dextran sulfate sodium-induced acute colitis. Lab. Invest. 2018, 98(4): 462-476. PubMed ID: 29330471
   
   

   The data presented in this article suggest that SLC26A3 may be one of the therapeutic targets of TNF-α. SLC26A3 plays a role in protecting the epithelial barrier and may be a therapeutic target in gut homeostasis.

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Reference

1. Lu Y C., et al. (2016) Involvement of Cl^-/HCO₃^- exchanger SLC26A3 and SLC26A6 in preimplantation embryo cleavage. Scientific Reports. 6: 28402.

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