SLC5A6 Membrane Protein Introduction

Introduction of SLC5A6

SLC5A6 is encoded by SLC5A6 gene. It belongs to the solute carrier family 5 which has been extensively studied during the past few decades because it offers numerous possibilities for therapeutic applications. SLC5A6 is involved in the transport of the water-soluble vitamin biotin. Besides this transporter is commonly referred to as the sodium-dependent multivitamin transporter (SMVT) because it also transports pantothenic acid and lipoic acid. Meanwhile, many studies conducted on SLC5A6 have shown that its variants are related to biotin deficiency and thiamine metabolism dysfunction syndrome.

Function of SLC5A6 Membrane Protein

SLC5A6, also named as sodium-dependent multivitamin transporter (SMVT), is expressed in various tissues such as placenta, intestine, brain, liver, lung, kidney, cornea, retina, and heart. It mediates biotin, pantothenic acid, and lipoate uptake in a variety of cellular systems. Recent studies have indicated that SLC5A6 is the only biotin uptake system that operates in the gut and that its deletion leads to biotin deficiency. In addition, some studies also confirm that intestinal-specific (conditional) knockout of the mouse Slc5a6 gene (SMVT-cKO) is associated with growth retardation, the development of spontaneous and severe inflammation, abnormal histology in the large intestine, altered gut permeability, and early death.

Fig.1 NIS models and SLC5 family alignment. (Ferrandino, 2016)

Application of SLC5A6 Membrane Protein in Literature

1. Sabui S., et al. Biotin and pantothenic acid oversupplementation to conditional SLC5A6 KO mice prevents the development of intestinal mucosal abnormalities and growth defects. Am J Physiol Cell Physiol. 2018, 315(1): C73-C79. PubMed ID: 29669219
   
   

   This article analyzes the function of biotin and pantothenic acid oversupplementation (BPS) in SMVT-cKO mice. These results indicate that biotin and BPS play an important role in the maintenance of normal intestinal integrity and health of SMVT-cKO mice.

2. Sabui S., et al. Role of the sodium-dependent multivitamin transporter (SMVT) in the maintenance of intestinal mucosal integrity. Am J Physiol Gastrointest Liver Physiol. 2016, 311(3): G561-70. PubMed ID: 27492331
   
   

   This article analyzes the role of SMVT in the maintenance of intestinal mucosal integrity and the expression level of tight junction (TJ) proteins. The results suggest dietary-induced biotin deficiency leads to a similar development of chronic active inflammation in the cecum with a change in the level of expression of TJ protein.

3. Uchida Y., et al. Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells. J Neurochem. 2015, 134(1): 97-112. PubMed ID: 25809983
   
   

   Authors in this group examine the expression level of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) and its contribution to the supply of biotin and pantothenic acid to the human brain via the blood-brain barrier. The data show that SLC5A6/SMVT is important to transport biotin and pantothenic acid into brain across the BBB in humans.

4. Subramanian V.S., et al. Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. Hum Genet. 2017, 136(2): 253-261. PubMed ID: 27904971
   
   

   This article examines the association between the SLC5A6 variants and brain, immune, bone, and intestinal dysfunction in a young child. The results suggest that the R123L mutant in SLC5A6 is important for brain development and a wide variety of clinical functions.

5. Ghosal A., et al. Conditional knockout of the Slc5a6 gene in mouse intestine impairs biotin absorption. Am J Physiol Gastrointest Liver Physiol. 2013, 304(1): G64-71. PubMed ID: 23104561
   
   

   This article examines the expression of SMVT in the intestine compared with sex-matched littermates as well as the expected normal SMVT expression in other tissues. The data demonstrate that SMVT is solely responsible for intestinal biotin uptake.

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Reference

1. Ferrandino G, et al. (2016). Na+ coordination at the Na2 site of the Na+/I- symporter. Proc Natl Acad Sci U S A. 113(37), E5379-88.

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