Transport of N-acetylaspartate by the Na+-dependent high-affinity dicarboxylate transporter NaDC3 and its relevance to the expression of the transporter in the brain

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 de tectable levels anywhere else in the body other than brain. Glial cells exp ress a high-affinity transporter for N-acetylaspartate, but the molecular i dentity of the transporter has not been established. The transport of N-ace tylaspartate into glial cells is obligatory for its intracellular hydrolysi s, a process intimately involved in myelination. N-Acetylaspartate is a dic arboxylate structurally related to succinate. We investigated in the presen t study the ability of NaDC3, a Na+-coupled high-affinity dicarboxylate tra nsporter, to transport N-acetylaspartate. The cloned rat and human NaDC3s w ere found to transport N-acetylaspartate in a Na+-coupled manner in two dif ferent heterologous expression systems. The Michaelis-Menten constant for N -acetylaspartate was similar to 60 mu M for rat NaDC3 and similar to 250 mu M for human NaDC3. The transport process was electrogenic and the Na+ :N-a cetylaspartate stoichiometry was 3:1. The functional expression of NaDC3 in the brain was demonstrated by in situ hybridization and reverse transcript ion-polymerase chain reaction as well as by isolation of a full-length func tional NaDC3 from a rat brain cDNA library. In addition, the expression of a Na+-coupled high-affinity dicarboxylate transporter and the interaction o f the transporter with N-acetylaspartate were demonstrable in rat primary a strocyte cultures. These studies establish NaDC3 as the transporter respons ible for the Na+-coupled transport of N-acetylaspartate in the brain. This transporter is likely to be an essential component in the metabolic role of N-acetylaspartate in the process of myelination.