Cloning and Sequencing of Four New Mammalian Monocarboxylate Transporter (MCT) Homologues Confirms the Existence of a Transporter Family with an Ancient Past

Overview

Journal Biochem J

Specialty Biochemistry

Date 1998 Feb 28

PMID 9425115

Citations 95

Authors

N T Price

V N Jackson

A P Halestrap

Affiliations

Soon will be listed here.

Abstract

Measurement of monocarboxylate transport kinetics in a range of cell types has provided strong circumstantial evidence for a family of monocarboxylate transporters (MCTs). Two mammalian MCT isoforms (MCT1 and MCT2) and a chicken isoform (REMP or MCT3) have already been cloned, sequenced and expressed, and another MCT-like sequence (XPCT) has been identified. Here we report the identification of new human MCT homologues in the database of expression sequence tags and the cloning and sequencing of four new full-length MCT-like sequences from human cDNA libraries, which we have denoted MCT3, MCT4, MCT5 and MCT6. Northern blotting revealed a unique tissue distribution for the expression of mRNA for each of the seven putative MCT isoforms (MCT1-MCT6 and XPCT). All sequences were predicted to have 12 transmembrane (TM) helical domains with a large intracellular loop between TM6 and TM7. Multiple sequence alignments showed identities ranging from 20% to 55%, with the greatest conservation in the predicted TM regions and more variation in the C-terminal than the N-terminal region. Searching of additional sequence databases identified candidate MCT homologues from the yeast Saccharomyces cerevisiae, the nematode worm Caenorhabditis elegans and the archaebacterium Sulfolobus solfataricus. Together these sequences constitute a new family of transporters with some strongly conserved sequence motifs, the possible functions of which are discussed.

Citing Articles

Role of Human Monocarboxylate Transporter 1 (hMCT1) and 4 (hMCT4) in Tumor Cells and the Tumor Microenvironment.

Liu T, Han S, Yao Y, Zhang G Cancer Manag Res. 2023; 15:957-975.

PMID: 37693221 PMC: 10487743. DOI: 10.2147/CMAR.S421771.

α-myosin heavy chain lactylation maintains sarcomeric structure and function and alleviates the development of heart failure.

Zhang N, Zhang Y, Xu J, Wang P, Wu B, Lu S Cell Res. 2023; 33(9):679-698.

PMID: 37443257 PMC: 10474270. DOI: 10.1038/s41422-023-00844-w.

The making of a potent L-lactate transport inhibitor.

Bosshart P, Kalbermatter D, Bonetti S, Fotiadis D Commun Chem. 2023; 4(1):128.

PMID: 36697570 PMC: 9814091. DOI: 10.1038/s42004-021-00564-5.

Lactate as a myokine and exerkine: drivers and signals of physiology and metabolism.

Brooks G, Osmond A, Arevalo J, Duong J, Curl C, Moreno-Santillan D J Appl Physiol (1985). 2023; 134(3):529-548.

PMID: 36633863 PMC: 9970662. DOI: 10.1152/japplphysiol.00497.2022.

Role and Clinical Significance of Monocarboxylate Transporter 8 (MCT8) During Pregnancy.

Thomas J, Sairoz , Jose A, Poojari V, Shetty S, Prasada K S Reprod Sci. 2023; 30(6):1758-1769.

PMID: 36595209 PMC: 10229697. DOI: 10.1007/s43032-022-01162-z.

References

Carpenter L, Halestrap A . The kinetics, substrate and inhibitor specificity of the lactate transporter of Ehrlich-Lettre tumour cells studied with the intracellular pH indicator BCECF. Biochem J. 1994; 304 ( Pt 3):751-60. PMC: 1137398. DOI: 10.1042/bj3040751. View

Lafreniere R, Carrel L, Willard H . A novel transmembrane transporter encoded by the XPCT gene in Xq13.2. Hum Mol Genet. 1994; 3(7):1133-9. DOI: 10.1093/hmg/3.7.1133. View

Garcia C, Li X, Luna J, Francke U . cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12. Genomics. 1994; 23(2):500-3. DOI: 10.1006/geno.1994.1532. View

Fliegel L, Dyck J . Molecular biology of the cardiac sodium/hydrogen exchanger. Cardiovasc Res. 1995; 29(2):155-9. View

Fleischmann R, Adams M, White O, Clayton R, Kirkness E, Kerlavage A . Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science. 1995; 269(5223):496-512. DOI: 10.1126/science.7542800. View

Philp N, Chu P, Pan T, Zhang R, Chu M, Stark K . Developmental expression and molecular cloning of REMP, a novel retinal epithelial membrane protein. Exp Cell Res. 1995; 219(1):64-73. DOI: 10.1006/excr.1995.1205. View

Jackson V, Price N, Halestrap A . cDNA cloning of MCT1, a monocarboxylate transporter from rat skeletal muscle. Biochim Biophys Acta. 1995; 1238(2):193-6. DOI: 10.1016/0005-2736(95)00160-5. View

Takanaga H, Tamai I, Inaba S, Sai Y, Higashida H, Yamamoto H . cDNA cloning and functional characterization of rat intestinal monocarboxylate transporter. Biochem Biophys Res Commun. 1995; 217(1):370-7. DOI: 10.1006/bbrc.1995.2786. View

Mallet L, Bussereau F, Jacquet M . A 43.5 kb segment of yeast chromosome XIV, which contains MFA2, MEP2, CAP/SRV2, NAM9, FKB1/FPR1/RBP1, MOM22 and CPT1, predicts an adenosine deaminase gene and 14 new open reading frames. Yeast. 1995; 11(12):1195-209. DOI: 10.1002/yea.320111210. View

10.

Jackson V, Halestrap A . The kinetics, substrate, and inhibitor specificity of the monocarboxylate (lactate) transporter of rat liver cells determined using the fluorescent intracellular pH indicator, 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. J Biol Chem. 1996; 271(2):861-8. DOI: 10.1074/jbc.271.2.861. View

11.

Carpenter L, POOLE R, Halestrap A . Cloning and sequencing of the monocarboxylate transporter from mouse Ehrlich Lettré tumour cell confirms its identity as MCT1 and demonstrates that glycosylation is not required for MCT1 function. Biochim Biophys Acta. 1996; 1279(2):157-63. DOI: 10.1016/0005-2736(95)00254-5. View

12.

Schmid C . Alu: structure, origin, evolution, significance and function of one-tenth of human DNA. Prog Nucleic Acid Res Mol Biol. 1996; 53:283-319. DOI: 10.1016/s0079-6603(08)60148-8. View

13.

Rechsteiner M, ROGERS S . PEST sequences and regulation by proteolysis. Trends Biochem Sci. 1996; 21(7):267-71. View

14.

Wang X, Levi A, Halestrap A . Substrate and inhibitor specificities of the monocarboxylate transporters of single rat heart cells. Am J Physiol. 1996; 270(2 Pt 2):H476-84. DOI: 10.1152/ajpheart.1996.270.2.H476. View

15.

Sensen C, Klenk H, Singh R, Allard G, Chan C, Liu Q . Organizational characteristics and information content of an archaeal genome: 156 kb of sequence from Sulfolobus solfataricus P2. Mol Microbiol. 1996; 22(1):175-91. DOI: 10.1111/j.1365-2958.1996.tb02666.x. View

16.

Yamane K, Kumano M, Kurita K . The 25 degrees-36 degrees region of the Bacillus subtilis chromosome: determination of the sequence of a 146 kb segment and identification of 113 genes. Microbiology (Reading). 1996; 142 ( Pt 11):3047-56. DOI: 10.1099/13500872-142-11-3047. View

17.

Arbuckle M, Kane S, Porter L, Seatter M, Gould G . Structure-function analysis of liver-type (GLUT2) and brain-type (GLUT3) glucose transporters: expression of chimeric transporters in Xenopus oocytes suggests an important role for putative transmembrane helix 7 in determining substrate selectivity. Biochemistry. 1996; 35(51):16519-27. DOI: 10.1021/bi962210n. View

18.

POOLE R, Sansom C, Halestrap A . Studies of the membrane topology of the rat erythrocyte H+/lactate cotransporter (MCT1). Biochem J. 1996; 320 ( Pt 3):817-24. PMC: 1218002. DOI: 10.1042/bj3200817. View

19.

Juel C . Lactate-proton cotransport in skeletal muscle. Physiol Rev. 1997; 77(2):321-58. DOI: 10.1152/physrev.1997.77.2.321. View

20.

Jackson V, Price N, Carpenter L, Halestrap A . Cloning of the monocarboxylate transporter isoform MCT2 from rat testis provides evidence that expression in tissues is species-specific and may involve post-transcriptional regulation. Biochem J. 1997; 324 ( Pt 2):447-53. PMC: 1218450. DOI: 10.1042/bj3240447. View