Cloning and functional characterization of a high-affinity Na(+)/dicarboxylate cotransporter from mouse brain.

Pajor AM, Gangula R, Yao X
Am J Physiol Cell Physiol. 2001 280 (5): C1215-23

PMID: 11287335 · DOI:10.1152/ajpcell.2001.280.5.C1215

Neurons contain a high-affinity Na(+)/dicarboxylate cotransporter for absorption of neurotransmitter precursor substrates, such as alpha-ketoglutarate and malate, which are subsequently metabolized to replenish pools of neurotransmitters, including glutamate. We have isolated the cDNA coding for a high-affinity Na(+)/dicarboxylate cotransporter from mouse brain, called mNaDC-3. The mRNA coding for mNaDC-3 is found in brain and choroid plexus as well as in kidney and liver. The mNaDC-3 transporter has a broad substrate specificity for dicarboxylates, including succinate, alpha-ketoglutarate, fumarate, malate, and dimethylsuccinate. The transport of citrate is relatively insensitive to pH, but the transport of succinate is inhibited by acidic pH. The Michaelis-Menten constant for succinate in mNaDC-3 is 140 microM in transport assays and 16 microM at -50 mV in two-electrode voltage clamp assays. Transport is dependent on sodium, although lithium can partially substitute for sodium. In conclusion, mNaDC-3 likely codes for the high-affinity Na(+)/dicarboxylate cotransporter in brain, and it has some unusual electrical properties compared with the other members of the family.

MeSH Terms (25)

Amino Acid Sequence Animals Brain Carrier Proteins Cloning, Molecular Consensus Sequence Female Fishes Gene Library Humans Kinetics Membrane Potentials Membrane Transport Proteins Mice Molecular Sequence Data Oocytes Rats Recombinant Proteins Reverse Transcriptase Polymerase Chain Reaction Sequence Alignment Sequence Homology, Amino Acid Substrate Specificity Succinates Symporters Xenopus laevis

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