Transport of N-acetylaspartate via murine sodium/dicarboxylate cotransporter NaDC3 and expression of this transporter and aspartoacylase II in ocular tissues in mouse.
Canavan disease is a genetic disorder associated with optic neuropathy and the metabolism of N-acetylaspartate is defective in this disorder due to mutations in the gene coding for the enzyme aspartoacylase II. Here we show that the plasma membrane transporter NaDC3, a Na+-coupled transporter for dicarboxylates, is able to transport N-acetylaspartate, suggesting that the transporter may function in concert with aspartoacylase II in the metabolism of N-acetylaspartate. Since Canavan disease is associated with ocular complications, we investigated the expression pattern of NaDC3 and aspartoacylase II in ocular tissues in mouse by in situ hybridization. These studies show that NaDC3 mRNA is expressed in the optic nerve, most layers of the retina, retinal pigment epithelium, ciliary body, iris, and lens. Aspartoacylase II mRNA is coexpressed in most of these cell types. We conclude that transport of N-acetylaspartate into ocular tissues via NaDC3 and its subsequent hydrolysis by aspartoacylase II play an essential role in the maintenance of visual function.
George
Ronald L
RL
Department of Physiology, Medical College of Georgia, Augusta, GA, USA.
Huang
Wei
W
Naggar
Hany A
HA
Smith
Sylvia B
SB
Ganapathy
Vadivel
V
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D001692:Biological Transport; D003001:Cloning, Molecular; D029382:Dicarboxylic Acid Transporters; D005123:Eye / Q000378:metabolism*; D017403:In Situ Hybridization; D051379:Mice; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013379:Substrate Specificity; D019802:Succinic Acid / Q000378:metabolism; D027981:Symporters / Q000378:metabolism
D029382:Dicarboxylic Acid Transporters; C492327:NaDC3 protein, mouse; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D027981:Symporters; D001224:Aspartic Acid; C000179:N-acetylaspartate; D019802:Succinic Acid; D000581:Amidohydrolases; C019751:aspartoacylase; C492328:aspartoacylase II, mouse