RT Journal Article
SR Electronic
T1 Transport of <em>N</em>-Acetylaspartate by the Na<sup>+</sup>-Dependent High-Affinity Dicarboxylate Transporter NaDC3 and Its Relevance to the Expression of the Transporter in the Brain
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 392
OP 403
VO 295
IS 1
A1 Wei Huang
A1 Haiping Wang
A1 Ramesh Kekuda
A1 You-Jun Fei
A1 Anne Friedrich
A1 Jian Wang
A1 Simon J. Conway
A1 Richard S. Cameron
A1 Frederick H. Leibach
A1 Vadivel Ganapathy
YR 2000
UL http://jpet.aspetjournals.org/content/295/1/392.abstract
AB N-Acetylaspartate is a highly specific marker for neurons and is present at high concentrations in the central nervous system. It is not present at detectable levels anywhere else in the body other than brain. Glial cells express a high-affinity transporter for N-acetylaspartate, but the molecular identity of the transporter has not been established. The transport ofN-acetylaspartate into glial cells is obligatory for its intracellular hydrolysis, a process intimately involved in myelination.N-Acetylaspartate is a dicarboxylate structurally related to succinate. We investigated in the present study the ability of NaDC3, a Na+-coupled high-affinity dicarboxylate transporter, to transport N-acetylaspartate. The cloned rat and human NaDC3s were found to transportN-acetylaspartate in a Na+-coupled manner in two different heterologous expression systems. The Michaelis-Menten constant for N-acetylaspartate was ∼60 μM for rat NaDC3 and ∼250 μM for human NaDC3. The transport process was electrogenic and the Na+:N-acetylaspartate stoichiometry was 3:1. The functional expression of NaDC3 in the brain was demonstrated by in situ hybridization and reverse transcription-polymerase chain reaction as well as by isolation of a full-length functional NaDC3 from a rat brain cDNA library. In addition, the expression of a Na+-coupled high-affinity dicarboxylate transporter and the interaction of the transporter withN-acetylaspartate were demonstrable in rat primary astrocyte cultures. These studies establish NaDC3 as the transporter responsible for the Na+-coupled transport ofN-acetylaspartate in the brain. This transporter is likely to be an essential component in the metabolic role ofN-acetylaspartate in the process of myelination. The American Society for Pharmacology and Experimental Therapeutics