SLC5A4 Membrane Protein Introduction

Introduction of SLC5A4

SLC5A4 (solute carrier family 5 member 4) also known as SAAT1or SGLT3 is a 72.5 kDa transmembrane protein that is composed of 659 amino acids. In humans, it is encoded by the SLC5A4 gene which resides on the chromosome 22q12.3. This low-affinity protein belongs to the sodium-glucose transport (SGLT) family whose members are cotransporters for sugars, vitamins, anions, and short-chain fatty acids. SLC5A4 is found in the small intestine and skeletal muscle. In the small intestine, it is expressed in cholinergic neurons in the submucosal and myenteric plexuses, but not in the enterocyte.

Function of SLC5A4 Membrane Protein

In SGLT family, SGLT1 (SLC5A1) is the most widely studied glucose/galactose transporter highly expressed in the small intestine. SGLT2 (SLC5A2) is a glucose transporter highly expressed in the kidney. SGLT3/SLC5A4 shares 70% amino acid identity to human SGLT1 and 56% to SGLT2. SLC5A4 is not as well characterized as these two better-known family members, while the properties of the human homolog have been found to be unique. Functional studies manifest that SLC5A4 is incapable of sugar transport, concluding it is not a Na(+)/glucose cotransporter but a glucose sensor on the plasma membranes of cholinergic neurons, skeletal muscle, together with other tissues. Electrophysiology studies indicate that glucose induces SLC5A4 to depolarize the plasma membrane in a saturable, Na(+)-dependent, phlorizin-sensitive manner. Additionally, it is also present on the skeletal muscle plasma membrane correlated with nicotinic acetylcholine receptors at the neuromuscular junctions. These data suggest a role for SLC5A4 as a glucose sensor modulating the activity of smooth and skeletal muscles.

Fig.1 Structure of Vibrio parahaemolyticus sodium/galactose symporter (vSGLT) viewed in the membrane plane. (Faham, 2008)

Application of SLC5A4 Membrane Protein in Literature

1. Lee E.Y., et al. Distinct action of the α-glucosidase inhibitor miglitol on SGLT3, enteroendocrine cells, and GLP1 secretion. J Endocrinol. 2015, 224(3): 205-214. PubMed ID: 25486965
   
   

   This article determined that though α-GIs normally delay carbohydrate absorption and potentiate glucagon-like peptide 1 (GLP1) secretion, miglitol can activate duodenal enterochromaffin (EC) cells, probably via SGLT3, and enhance GLP1 secretion by the parasympathetic nervous system.

2. Han J.Y., et al. Whole-genome analysis of a patient with early-stage small-cell lung cancer. Pharmacogenomics J. 2014, 14(6): 503-508. PubMed ID: 24709692
   
   

   The whole-genome sequencing of a case of early-stage small-cell lung cancer (SCLC) has been performed to analyze the genomic features. Sanger sequencing of SLC5A4 gene in twenty-three independent SCLC specimens showed another novel nonsynonymous single-nucleotide variations (nsSNVs) in the SLC5A4 gene, indicating nsSNVs in the SLC5A4 gene are recurrent in SCLC.

3. Kadam R.S., et al. Hypoxia alters ocular drug transporter expression and activity in rat and calf models: implications for drug delivery. Mol Pharm. 2013, 10(6): 2350-2361. PubMed ID: 23607566
   
   

   The aim of this study was to identify the effect of chronic hypoxia on drug transporter mRNA expression and activity in ocular barriers. The 84 transporters in rat choroid-retina revealed that 29 transporter genes are upregulated or downregulated by more than 1.5-fold in hypoxia. Among them, 11 transporters including SLC10a1, SLC5a4, SLC7a11, etc. are upregulated.

4. Fowler K.E., et al. Genome wide analysis reveals single nucleotide polymorphisms associated with fatness and putative novel copy number variants in three pig breeds. BMC Genomics. 2013, 14: 784. PubMed ID: 24225222
   
   

   This study identified SNPs and CNVs associated with fatness and with estimated major effects in a large population of animals.

5. Kothinti R.K., et al. A novel SGLT is expressed in the human kidney. Eur J Pharmacol. 2012, 690(1-3): 77-83. PubMed ID: 22766068
   
   

   The present studies tested the mRNA and protein expression of SGLT3 in human kidney and proximal tubule HK-2 cell line. The results revealed that human SGLT3 (hSGLT3) message and protein were present both in vivo and in vitro.

SLC5A4 Preparation Options

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Reference

1. Faham S, et al. (2008). The crystal structure of a sodium galactose transporter reveals mechanistic insights into Na+/sugar symport. Science. 321(5890), 810-814.

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