Biology:SLC5A1

Generic protein structure example

Sodium/glucose cotransporter 1 also known as solute carrier family 5 member 1 is a protein that in humans is encoded by the SLC5A1 gene.

Function

Glucose transporters are integral membrane proteins that mediate the transport of glucose and structurally related substances across cellular membranes. The role of the sodium-glucose cotransporters is to not only absorb glucose, but to also absorb sodium and to then reabsorb the sodium and glucose from the tubule of the nephron. Two families of glucose transporter have been identified: the facilitated diffusion glucose transporter family (GLUT family), also known as 'uniporters,' and the sodium-dependent glucose transporter family (SGLT family), also known as 'cotransporters' or 'symporters. The SLC5A1 gene encodes a protein that is involved in the active transport of glucose and galactose into eukaryotic and some prokaryotic cells.

Cloning

Co-transport proteins of mammalian cell membranes had eluded efforts of purification with classical biochemical methods until the late 1980s. These proteins had proven difficult to isolate because they contain hydrophilic and hydrophobic sequences and exist in membranes only in very low abundance (<0.2% of membrane proteins). The rabbit form of SGLT1 was the first mammalian co-transport protein ever to be cloned and sequenced, and this was reported in 1987. To circumvent the difficulties with traditional isolation methods, a novel expression cloning technique was used. Size-fractionation of large amounts of rabbit intestinal mRNA with preparative gel electrophoresis were then sequentially injected into Xenopus oocytes to ultimately find the RNA species that induced the expression of sodium-glucose cotransport.

Mutations

SLC5A1 is important because of its role in the absorption of glucose and sodium, however, mutations in the gene can cause serious effects. A mutation in the SLC5A1 gene can cause problems creating the SGLT1 protein, leading to a rare glucose-galactose malabsorption disease. Glucose-galactose malabsorption occurs when the lining of the intestinal cells can't take in glucose and galactose which prevents the use of those molecules in catabolism and anabolism. The disease has symptoms that consist of watery and/or acidic diarrhea which is the result of water retention in the intestinal lumen and osmotic loss created by non-absorbed glucose, galactose and sodium. Glucose-Galactose malabsorption can cause death, due to loss of water from diarrhea, if the disease isn't treated soon. To counteract the disease, oral rehydration therapy is performed using sodium, glucose, and water for intestinal reabsorption.

Tissue distribution

The SLC5A1 cotransporter is mainly expressed in the lumen of the small intestine, kidney, parotid glands, submandibular glands and in the heart.

See also

• Solute carrier family
• SGLT Family
• SGLT2

Interactions

SLC5A1 has been shown to interact with PAWR.

Further reading

• "The human plasma proteome: history, character, and diagnostic prospects". Molecular & Cellular Proteomics 1 (11): 845–867. 2003. doi:10.1074/mcp.R200007-MCP200. PMID 12488461. 
• "Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter". Nature 350 (6316): 354–356. 1991. doi:10.1038/350354a0. PMID 2008213. 
• "Homology of the human intestinal Na+/glucose and Escherichia coli Na+/proline cotransporters". Proceedings of the National Academy of Sciences of the United States of America 86 (15): 5748–5752. 1989. doi:10.1073/pnas.86.15.5748. PMID 2490366. 
• "The development of Na(+)-dependent glucose transport during differentiation of an intestinal epithelial cell clone is regulated by protein kinase C". Journal of Biological Chemistry 270 (21): 12536–12541. 1995. doi:10.1074/jbc.270.21.12536. PMID 7759499. 
• "Assignment of the human Na+/glucose cotransporter gene SGLT1 to chromosome 22q13.1". Genomics 17 (3): 752–754. 1993. doi:10.1006/geno.1993.1399. PMID 8244393. 
• "Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption". Nature Genetics 12 (2): 216–220. 1996. doi:10.1038/ng0296-216. PMID 8563765. 
• "Membrane topology of the human Na+/glucose cotransporter SGLT1". Journal of Biological Chemistry 271 (4): 1925–1934. 1996. doi:10.1074/jbc.271.4.1925. PMID 8567640. 
• "Missense mutations in SGLT1 cause glucose-galactose malabsorption by trafficking defects". Biochimica et Biophysica Acta 1453 (2): 297–303. 1999. doi:10.1016/s0925-4439(98)00109-4. PMID 10036327. 
• "The DNA sequence of human chromosome 22". Nature 402 (6761): 489–495. 1999. doi:10.1038/990031. PMID 10591208. 
• "Expression of glucose transporters in lactating human mammary gland epithelial cells". European Journal of Nutrition 39 (5): 194–200. 2001. doi:10.1007/s003940070011. PMID 11131365. 
• "A missense mutation in the Na(+)/glucose cotransporter gene SGLT1 in a patient with congenital glucose-galactose malabsorption: normal trafficking but inactivation of the mutant protein". Biochimica et Biophysica Acta 1536 (2–3): 141–147. 2001. doi:10.1016/s0925-4439(01)00043-6. PMID 11406349. 
• "New human sodium/glucose cotransporter gene (KST1): identification, characterization, and mutation analysis in ICCA (infantile convulsions and choreoathetosis) and BFIC (benign familial infantile convulsions) families". Gene 285 (1–2): 141–148. 2002. doi:10.1016/S0378-1119(02)00416-X. PMID 12039040. 
• "Up-regulation of sodium-dependent glucose transporter by interaction with heat shock protein 70". Journal of Biological Chemistry 277 (36): 33338–33343. 2002. doi:10.1074/jbc.M200310200. PMID 12082088. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.