Cloning and functional identification of slc5a12 as a sodium-coupled low-affinity transporter for monocarboxylates (SMCT2)

Sonne R. Srinivas, Elangovan Gopal, Lina Zhuang, Shirou Itagaki, Pamela Moore Martin, You Jun Fei, Vadivel Ganapathy, Puttur D Prasad

Research output: Contribution to journalArticle

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Abstract

We report in the present paper, on the isolation and functional characterization of slc5a12, the twelfth member of the SLC5 gene family, from mouse kidney. The slc5a12 cDNA codes for a protein of 619 amino acids. Heterologous expression of slc5a12 cDNA in mammalian cells induces Na +-dependent transport of lactate and nicotinate. Several other short-chain monocarboxylates compete with nicotinate for the cDNA-induced transport process. Expression of slc5a12 in Xenopus oocytes induces electrogenic and Na+-dependent transport of lactate, nicotinate, propionate and butyrate. The substrate specificity of slc5a12 is similar to that of slc5a8, an Na+-coupled transporter for monocarboxylates. However, the substrate affinities of slc5a12 were much lower than those of slc5a8. slc5a12 mRNA is expressed in kidney, small intestine and skeletal muscle. In situ hybridization with sagittal sections of mouse kidney showed predominant expression of slc5a12 in the outer cortex. This is in contrast with slc5a8, which is expressed in the cortex as well as in the medulla. The physiological function of slc5a12 in the kidney is likely to mediate the reabsorption of lactate. In the intestinal tract, slc5a12 is expressed in the proximal parts, whereas slc5a8 is expressed in the distal parts. The expression of slc5a12 in the proximal parts of the intestinal tract, where there is minimal bacterial colonization, suggests that the physiological function of slc5a12 is not to mediate the absorption of short-chain monocarboxylates derived from bacterial fermentation but rather to mediate the absorption of diet-derived short-chain monocarboxylates. Based on the functional and structural similarities between slc5a8 and slc5a12, we suggest that the two transporters be designated as SMCT1 (sodium-coupled monocarboxylate transporter 1) and SMCT2 respectively.

Original languageEnglish (US)
Pages (from-to)655-664
Number of pages10
JournalBiochemical Journal
Volume392
Issue number3
DOIs
StatePublished - Dec 15 2005

Fingerprint

Cloning
Niacin
Organism Cloning
Lactic Acid
Complementary DNA
Sodium
Kidney
Butyrates
Propionates
Substrates
Nutrition
Fermentation
Muscle
Substrate Specificity
Xenopus
Genes
Cells
Small Intestine
Oocytes
In Situ Hybridization

Keywords

  • Cloning
  • Functional characterization
  • Low-affinity monocarboxylate transport
  • SLC5
  • Sodium-coupled monocarboxylate transporter
  • Xenopus laevis oocyte

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Cloning and functional identification of slc5a12 as a sodium-coupled low-affinity transporter for monocarboxylates (SMCT2). / Srinivas, Sonne R.; Gopal, Elangovan; Zhuang, Lina; Itagaki, Shirou; Martin, Pamela Moore; Fei, You Jun; Ganapathy, Vadivel; Prasad, Puttur D.

In: Biochemical Journal, Vol. 392, No. 3, 15.12.2005, p. 655-664.

Research output: Contribution to journalArticle

Srinivas, Sonne R. ; Gopal, Elangovan ; Zhuang, Lina ; Itagaki, Shirou ; Martin, Pamela Moore ; Fei, You Jun ; Ganapathy, Vadivel ; Prasad, Puttur D. / Cloning and functional identification of slc5a12 as a sodium-coupled low-affinity transporter for monocarboxylates (SMCT2). In: Biochemical Journal. 2005 ; Vol. 392, No. 3. pp. 655-664.
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AU - Gopal, Elangovan

AU - Zhuang, Lina

AU - Itagaki, Shirou

AU - Martin, Pamela Moore

AU - Fei, You Jun

AU - Ganapathy, Vadivel

AU - Prasad, Puttur D

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KW - Xenopus laevis oocyte

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