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Originally published In Press as doi:10.1074/jbc.M208763200 on December 11, 2002

J. Biol. Chem., Vol. 278, Issue 8, 6136-6144, February 21, 2003
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Structural and Functional Characteristics of Two Sodium-coupled Dicarboxylate Transporters (ceNaDC1 and ceNaDC2) from Caenorhabditis elegans and Their Relevance to Life Span*

You-Jun FeiDagger §, Katsuhisa InoueDagger , and Vadivel GanapathyDagger

From the Departments of Dagger  Biochemistry and Molecular Biology, and  Obstetrics and Gynecology, Medical College of Georgia, Augusta, Georgia 30912

We have cloned and functionally characterized two Na+-coupled dicarboxylate transporters, namely ceNaDC1 and ceNaDC2, from Caenorhabditis elegans. These two transporters show significant sequence homology with the product of the Indy gene identified in Drosophila melanogaster and with the Na+-coupled dicarboxylate transporters NaDC1 and NaDC3 identified in mammals. In a mammalian cell heterologous expression system, the cloned ceNaDC1 and ceNaDC2 mediate Na+-coupled transport of various dicarboxylates. With succinate as the substrate, ceNaDC1 exhibits much lower affinity compared with ceNaDC2. Thus, ceNaDC1 and ceNaDC2 correspond at the functional level to the mammalian NaDC1 and NaDC3, respectively. The nadc1 and nadc2 genes are not expressed at the embryonic stage, but the expression is detectable all through the early larva stage to the adult stage. Tissue-specific expression pattern studies using a reporter gene fusion approach in transgenic C. elegans show that both genes are coexpressed in the intestinal tract, an organ responsible for not only the digestion and absorption of nutrients but also for the storage of energy in this organism. Independent knockdown of the function of these two transporters in C. elegans using the strategy of RNA interference suggests that NaDC1 is not associated with the regulation of average life span in this organism, whereas the knockdown of NaDC2 function leads to a significant increase in the average life span. Disruption of the function of the high affinity Na+-coupled dicarboxylate transporter NaDC2 in C. elegans may lead to decreased availability of dicarboxylates for cellular production of metabolic energy, thus creating a biological state similar to that of caloric restriction, and consequently leading to life span extension.


* This work was supported by National Institutes of Health Grants DA10065 and HD33347 (to V. G.) and by an intramural grant from the Medical College of Georgia Research Institute (to Y. J. F.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ To whom correspondence should be addressed. E-mail: yjfei@mail.mcg.edu.


Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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