SLC4A7 Membrane Protein Introduction

Introduction of SLC4A7

Solute carrier family 4, member 7 (SLC4A7), also known as NBC3, is encoded by SLC4A7 gene. It is a transmembrane protein that transport sodium and bicarbonate ions in a 1:1 ratio and plays an important role in the regulation of bicarbonate secretion/absorption and intracellular pH. SLC4A7 is widely expressed in testis, spleen, retina, colon, small intestine, ovary, thymus, prostate, muscle, heart, and kidney.

Function of SLC4A7 Membrane Protein

SLC4A7 functions as a sodium bicarbonate cotransporter that mediates the coupled movement of sodium and bicarbonate ions across the plasma membrane of many cells. SLC4A7 is an electroneutral cotransporter that transports sodium and bicarbonate ions in a 1:1 ratio. SLC4A7 participates in the regulation of intracellular pH associated with visual and auditory sensory transmission. And SLC4A7 is also involved in the bicarbonate salvage in secretory epithelia. Moreover, SLC4A7 has been indicated a role in phagosome acidification. Loss function of SLC4A7 leads to increased cytoplasmic acidification during phagocytosis, which suggests that SLC4A7-mediated, bicarbonate-driven maintenance of cytoplasmic pH is required for phagosome acidification. Furthermore, SLC4A7 may be associated with the progression of tumors. It has been reported that SLC4A7 can promote acid extrusion from breast cancer tissues, sustain the alkaline intracellular environment and facilitate aggressive cancer development and growth. In addition, SLC4A7 also participates in the acid extrusion of vascular smooth muscle cells and involves the regulation of blood pressure.

Fig.1 Putative models of topological organization of SLC4 transporters (A, B) and 3D crystal structure of Nt domain of AE1 (C). (Ying, 2015)

Application of SLC4A7 Membrane Protein in Literature

1. Boedtkjer E., et al. Contribution of Na⁺, HCO3(-)-cotransport to cellular pH control in human breast cancer: a role for the breast cancer susceptibility locus NBCn1 (SLC4A7). International Journal of Cancer. 2013, 132(6):1288-1299. PubMed ID: 22907202
   
   

   The study shows that the expression of SLC4A7 is increased in human primary breast carcinomas and metastases compared to normal breast tissue. Besides, SLC4A7 is a major determinant of pH(i) in breast cancer.

2. Chen W., et al. The SLC4A7 variant rs4973768 is associated with breast cancer risk: evidence from a case-control study and a meta-analysis. Breast Cancer Research & Treatment. 2012, 136(3):847-857. PubMed ID: 23117855
   
   

   In the hospital-based case-control study, results indicate that a genetic variant rs4973768, located in 3'-UTR of SLC4A7 is associated with the risk of breast cancer.

3. Fu L.N., et al. Increased NBCn1 expression, Na⁺/ co-transport and intracellular pH in human vascular smooth muscle cells with a risk allele for hypertension. Human Molecular Genetics. 2017, 26(5):989-1002. PubMed ID: 28087731
   
   

   The findings show a genotypic effect on SLC4A7 expression and pHi regulation in vascular smooth muscle cells, which supports the molecular mechanism underlying the association with variation at the SLC4A7 locus with blood pressure.

4. Lee S., et al. Na⁺, HCO3^- -cotransport is functionally upregulated during human breast carcinogenesis and required for the inverted pH gradient across the plasma membrane. Pflugers Archiv European Journal of Physiology. 2015, 467(2):367-377. PubMed ID: 24788003
   
   

   The article reveals that the acid distribution mediated by SLC4A7 may play a pathophysiological role in breast cancer development and progression.

5. Lee C.Y., et al. Functional characterization of intracellular pH regulators responsible for acid extrusion in human radial artery smooth muscle cells. Chinese Journal of Physiology. 2014, 57(5):238-248. PubMed ID: 25241983
   
   

   The research demonstrates, for the first time, that NHE and NBC, as well as MCT are responsible for the regulation of acid extrusion, and these regulators are functionally co-existed in cultured human radial artery smooth muscle cells.

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Reference

1. Ying L, et al. (2015). Structure and function of SLC4 family HCO3− transporters. Frontiers in Physiology. 6: 355.

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