MFSD4B Membrane Protein Introduction

Introduction of MFSD4B

Sodium-dependent glucose transporter 1 (SGLT1), also known as MFSD4B, belongs to the SGLT family encoded by the MFSD4B gene predominantly expressed in the small intestine. The SGLT family consists of several isoforms that actively transport sugar through the cell membrane, and this process combines with sodium transport. SGLT1 is mainly expressed in the gastrointestinal tract and is mainly responsible for the absorption of glucose and galactose by the intestinal tract. In addition, MFSD4B is also present in the proximal straight tube of the kidney, which helps to absorb plasma glucose filtered from the blood. Under low glucose conditions, the expression of MFSD4B in the small intestine is down-regulated, mRNA expression level is also reduced, and MFSD4B function is impaired as well. Under dietary conditions, pancreatic MFSD4B mRNA did not change, indicating MFSD4B has different regulatory mechanisms in different tissues.

Function of MFSD4B Membrane Protein

Glucose transport across mammalian cell membranes is mediated either by facilitative glucose transporter (GLUT) or by SGLT1 (MFSD4B) and other SGLTs. The GLUT-mediated pathway is accomplished by passive diffusion of glucose. In contrast, MFSD4B-mediated transport is driven by sodium and glucose gradients, thus allowing glucose to move against its concentration gradient. In addition, MFSD4B is associated with detergent-resistant membrane microdomains. By disrupting these detergent-resistant membrane microdomains with methyl-β-cyclodextrin, the abundance of MFSD4B proteins in these microdomains is reduced and paralleled by a decrease of sodium-dependent glucose transport activity. Furthermore, MFSD4B is involved in the repair of plasma membrane integrity and tight junction integrity injured by heat stress and can reduce peroxynitrite and cell injury caused by cisplatin in renal tubular epithelial cells. Last but not the least, MFSD4B provides protection against damage induced by TLR ligands, in intestinal epithelial cells and in a murine model of septic shock. Thus, activated MFSD4B may be a promising target for inhibition of bacterial-induced inflammatory processes and life-saving treatments.

Fig.1 In the distal lung epithelium, glucose uptake across the apical membrane is through sodium-coupled glucose transporter SGLT1 and the basolateral membrane through GLUTs. (Garnett, 2012)

Application of MFSD4B Membrane Protein in Literature

1. Lapuerta P., et al. Development of sotagliflozin, a dual sodium-dependent glucose transporter 1/2 inhibitor. Diabetes & Vascular Disease Research. 2015, 12(2): 101-10. PubMed ID: 25690134
   
   

   This article finds that the different clinical features of a dual inhibitor of SGLT1 and SGLT2 may have clinical implications for the use of canagliflozin in the treatment of both type 1 and type 2 diabetes.

2. Wang Y., et al. Gymnemic acids inhibit sodium-dependent glucose transporter 1. Journal of Agricultural & Food Chemistry. 2014, 62(25): 5925-31. PubMed ID: 24856809
   
   

   This article shows that high levels of SGLT1 in the brush border membrane of intestinal epithelial cells, and saponins have the potential for inhibiting glucose uptake in the gastrointestinal tract.

3. Ikari A., et al. Sodium-dependent glucose transporter reduces peroxynitrite and cell injury caused by cisplatin in renal tubular epithelial cells. Biochimica et Biophysica Acta. 2005, 1717(2): 0-117. PubMed ID: 16288972
   
   

   This article indicates that peroxynitrite is the main mediator of nephrotoxicity caused by high-dose cisplatin, and SGLT1 endogenously exerts cytoprotective effects by reducing the production of peroxynitrite.

4. Palazzo M., et al. Sodium-dependent glucose transporter-1 as a novel immunological player in the intestinal mucosa. The Journal of Immunology. 2008, 181(5): 3126-3136. PubMed ID: 18713983
   
   

   This article proposes that activated SGLT-1, apart from its classical metabolic function, may be a promising target for inhibition of bacteria-induced inflammatory processes and life-saving treatments, assuming a novel role as an immunological player.

5. Di F.A., et al. Sodium-dependent glucose transporters (SGLT) in human ischemic heart: A new potential pharmacological target. International Journal of Cardiology. 2017, 243: 86-90. PubMed ID: 28526540
   
   

   This article reveals the possibility that over-expressed SGLT1 in cardiomyocytes may represent a potential pharmacological target for cardioprotection.

MFSD4B Preparation Options

Membrane protein studies have advanced significantly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms as well as multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-MFSD4B antibody development services.

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

During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

1. Garnett J P, et al. (2012). Sweet talk: insights into the nature and importance of glucose transport in lung epithelium. European Respiratory Journal. 40(5): 1269-1276.

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