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.
Biochem J
2003 Dec 01;376Pt 2:413-22. doi: 10.1042/BJ20030799.
Show Gene links
Show Anatomy links
The loop between helix 4 and helix 5 in the monocarboxylate transporter MCT1 is important for substrate selection and protein stability.
Gali S, Schneider HP, Bröer A, Deitmer JW, Bröer S.
???displayArticle.abstract???
Transport of lactate, pyruvate and the ketone bodies acetoacetate and beta-hydroxybutyrate, is mediated in most mammalian cells by members of the monocarboxylate transporter family (SLC16). A conserved signature sequence has been identified in this family, which is located in the loop between helix 4 and helix 5 and extends into helix 5. We have mutated residues in this signature sequence in the rat monocarboxylate transporter (MCT1) to elucidate the significance of this region for monocarboxylate transport. Mutation of R143 and G153 resulted in complete inactivation of the transporter. For the MCT1(G153V) mutant this was explained by a failure to reach the plasma membrane. The lack of transport activity of MCT1(R143Q) could be partially rescued by the conservative exchange R143H. The resulting mutant transporter displayed reduced stability, a decreased V (max) of lactate transport but not of acetate transport, and an increased stereoselectivity. Mutation of K137, K141 and K142 indicated that only K142 played a significant role in the transport mechanism. Mutation of K142 to glutamine resulted in an increase of the K (m) for lactate from 5 mM to 12 mM. In contrast with MCT1(R143H), MCT1(K142Q) was less stereoselective than the wild-type. A mechanism is proposed that includes all critical residues.
Abramson,
Structure and mechanism of the lactose permease of Escherichia coli.
2003, Pubmed
Abramson,
Structure and mechanism of the lactose permease of Escherichia coli.
2003,
Pubmed Bröer,
Xenopus laevis Oocytes.
2003,
Pubmed
,
Xenbase Bröer,
Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH.
1998,
Pubmed
,
Xenbase 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 Carpenter,
The kinetics, substrate and inhibitor specificity of the lactate transporter of Ehrlich-Lettre tumour cells studied with the intracellular pH indicator BCECF.
1994,
Pubmed Chillarón,
An intracellular trafficking defect in type I cystinuria rBAT mutants M467T and M467K.
1997,
Pubmed
,
Xenbase De Bruijne,
Kinetic analysis of L-lactate transport in human erythrocytes via the monocarboxylate-specific carrier system.
1983,
Pubmed Deuticke,
Monocarboxylate transport in erythrocytes.
1982,
Pubmed Garcia,
cDNA cloning of MCT2, a second monocarboxylate transporter expressed in different cells than MCT1.
1995,
Pubmed Garcia,
Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle.
1994,
Pubmed Halestrap,
The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation.
1999,
Pubmed
,
Xenbase Jung,
Role of glycine residues in the structure and function of lactose permease, an Escherichia coli membrane transport protein.
1995,
Pubmed Merickel,
Charged residues in transmembrane domains II and XI of a vesicular monoamine transporter form a charge pair that promotes high affinity substrate recognition.
1997,
Pubmed Munsch,
Sodium-bicarbonate cotransport current in identified leech glial cells.
1994,
Pubmed Pierre,
Cell-specific localization of monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain revealed by double immunohistochemical labeling and confocal microscopy.
2000,
Pubmed Poole,
Studies of the membrane topology of the rat erythrocyte H+/lactate cotransporter (MCT1).
1996,
Pubmed Price,
Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past.
1998,
Pubmed Rahman,
Helix 8 and helix 10 are involved in substrate recognition in the rat monocarboxylate transporter MCT1.
1999,
Pubmed
,
Xenbase Wilson,
Fluorescence resonance energy transfer studies on the interaction between the lactate transporter MCT1 and CD147 provide information on the topology and stoichiometry of the complex in situ.
2002,
Pubmed
