Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Physiol
2004 Jun 15;557Pt 3:719-31. doi: 10.1113/jphysiol.2004.063859.
Show Gene links
Show Anatomy links
The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter.
Coady MJ
,
Chang MH
,
Charron FM
,
Plata C
,
Wallendorff B
,
Sah JF
,
Markowitz SD
,
Romero MF
,
Lapointe JY
.
???displayArticle.abstract???
The orphan cotransport protein expressed by the SLC5A8 gene has been shown to play a role in controlling the growth of colon cancers, and the silencing of this gene is a common and early event in human colon neoplasia. We expressed this protein in Xenopus laevis oocytes and have found that it transports small monocarboxylic acids. The electrogenic activity of the cotransporter, which we have named SMCT (sodium monocarboxylate transporter), was dependent on external Na(+) and was compatible with a 3 : 1 stoichiometry between Na(+) and monocarboxylates. A portion of the SMCT-mediated current was also Cl(-) dependent, but Cl(-) was not cotransported. SMCT transports a variety of monocarboxylates (similar to unrelated monocarboxylate transport proteins) and most transported monocarboxylates demonstrated K(m) values near 100 microm, apart from acetate and d-lactate, for which the protein showed less affinity. SMCT was strongly inhibited by 1 mm probenecid or ibuprofen. In the absence of external substrate, a Na(+)-independent leak current was also observed to pass through SMCT. SMCT activity was strongly inhibited after prolonged exposure to high external concentrations of monocarboxylates. The transport of monocarboxylates in anionic form was confirmed by the observation of a concomitant alkalinization of the cytosol. SMCT, being expressed in colon and kidney, represents a novel means by which Na(+), short-chain fatty acids and other monocarboxylates are transported in these tissues. The significance of a Na(+)-monocarboxylate transporter to colon cancer presumably stems from the transport of butyrate, which is well known for having anti-proliferative and apoptosis-inducing activity in colon epithelial cells.
Al-Awqati,
One hundred years of membrane permeability: does Overton still rule?
1999, Pubmed
Al-Awqati,
One hundred years of membrane permeability: does Overton still rule?
1999,
Pubmed
Bachowska-Mac,
Transport of alpha-ketoisocaproate in neuroblastoma NB-2a cells.
1997,
Pubmed
Barac-Nieto,
Asymmetry in the transport of lactate by basolateral and brush border membranes of rat kidney cortex.
1982,
Pubmed
Bröer,
Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes.
1999,
Pubmed
,
Xenbase
Bröer,
Comparison of lactate transport in astroglial cells and monocarboxylate transporter 1 (MCT 1) expressing Xenopus laevis oocytes. Expression of two different monocarboxylate transporters in astroglial cells and neurons.
1997,
Pubmed
,
Xenbase
Chen,
Thermodynamic determination of the Na+: glucose coupling ratio for the human SGLT1 cotransporter.
1995,
Pubmed
,
Xenbase
Chu,
Transepithelial SCFA fluxes link intracellular and extracellular pH regulation of mouse colonocytes.
1997,
Pubmed
Coady,
Identification of a novel Na+/myo-inositol cotransporter.
2002,
Pubmed
,
Xenbase
Dai,
Cloning and characterization of the thyroid iodide transporter.
1996,
Pubmed
,
Xenbase
Diez-Sampedro,
A glucose sensor hiding in a family of transporters.
2003,
Pubmed
,
Xenbase
Eskandari,
Thyroid Na+/I- symporter. Mechanism, stoichiometry, and specificity.
1997,
Pubmed
,
Xenbase
Flagg,
Molecular mechanism of a COOH-terminal gating determinant in the ROMK channel revealed by a Bartter's disease mutation.
2002,
Pubmed
,
Xenbase
Halestrap,
The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond.
2004,
Pubmed
Heerdt,
Potentiation by specific short-chain fatty acids of differentiation and apoptosis in human colonic carcinoma cell lines.
1994,
Pubmed
Holtug,
Experimental studies of intestinal ion and water transport.
1996,
Pubmed
Kaluz,
Directional cloning of PCR products using exonuclease III.
1992,
Pubmed
Kenyon,
Lactate transport mechanisms at apical and basolateral membranes of bovine retinal pigment epithelium.
1994,
Pubmed
Kunzelmann,
Electrolyte transport in the mammalian colon: mechanisms and implications for disease.
2002,
Pubmed
Li,
SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers.
2003,
Pubmed
Loo,
Role of Cl- in electrogenic Na+-coupled cotransporters GAT1 and SGLT1.
2000,
Pubmed
,
Xenbase
Mengual,
Kinetic asymmetry of renal Na+-L-lactate cotransport. Characteristic parameters and evidence for a ping pong mechanism of the trans-stimulating exchange by pyruvate.
1990,
Pubmed
Nakhoul,
Acetate transport in the S3 segment of the rabbit proximal tubule and its effect on intracellular pH.
1988,
Pubmed
Nord,
Specificity of the Na+-dependent monocarboxylic acid transport pathway in rabbit renal brush border membranes.
1983,
Pubmed
Okuda,
Identification and characterization of the high-affinity choline transporter.
2000,
Pubmed
Parent,
Electrogenic properties of the cloned Na+/glucose cotransporter: I. Voltage-clamp studies.
1992,
Pubmed
,
Xenbase
Poole,
Transport of lactate and other monocarboxylates across mammalian plasma membranes.
1993,
Pubmed
Poustis-Delpont,
LLC-PK1 cells express Na+-lactate cotransport in apical membranes after confluency.
1988,
Pubmed
Prasad,
Cloning and functional expression of a cDNA encoding a mammalian sodium-dependent vitamin transporter mediating the uptake of pantothenate, biotin, and lipoate.
1998,
Pubmed
Ritzhaupt,
Identification and characterization of a monocarboxylate transporter (MCT1) in pig and human colon: its potential to transport L-lactate as well as butyrate.
1998,
Pubmed
Rodriguez,
Identification and characterization of a putative human iodide transporter located at the apical membrane of thyrocytes.
2002,
Pubmed
Romero,
Cloning and functional expression of rNBC, an electrogenic Na(+)-HCO3- cotransporter from rat kidney.
1998,
Pubmed
,
Xenbase
Romero,
Expression cloning and characterization of a renal electrogenic Na+/HCO3- cotransporter.
1997,
Pubmed
,
Xenbase
Schröder,
Substrate and inhibitor specificity of butyrate uptake in apical membrane vesicles of the rat distal colon.
2000,
Pubmed
Sellin,
SCFAs: The Enigma of Weak Electrolyte Transport in the Colon.
1999,
Pubmed
Siebens,
Depolarization-induced alkalinization in proximal tubules. II. Effects of lactate and SITS.
1989,
Pubmed
Stewart,
Regulation of AE2 anion exchanger by intracellular pH: critical regions of the NH(2)-terminal cytoplasmic domain.
2001,
Pubmed
,
Xenbase
Storelli,
Polar distribution of sodium-dependent and sodium-independent transport system for L-lactate in the plasma membrane of rat enterocytes.
1980,
Pubmed
Ullrich,
Reabsorption of monocarboxylic acids in the proximal tubule of the rat kidney. III. Specificity for aromatic compounds.
1982,
Pubmed
Ullrich,
Reabsorption of monocarboxylic acids in the proximal tubule of the rat kidney. II. Specificity for aliphatic compounds.
1982,
Pubmed
Umbach,
Intestinal Na+/glucose cotransporter expressed in Xenopus oocytes is electrogenic.
1990,
Pubmed
,
Xenbase
Wright,
The sodium/glucose cotransport family SLC5.
2004,
Pubmed
Wright,
Transport of carboxylic acids by renal membrane vesicles.
1985,
Pubmed
Zaharia,
Effects of short chain fatty acids on colonic Na+ absorption and enzyme activity.
2001,
Pubmed
