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J. Biol. Chem., Vol. 278, Issue 8, 6136-6144, February 21, 2003
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From the Departments of 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.
Structural and Functional Characteristics of Two Sodium-coupled
Dicarboxylate Transporters (ceNaDC1 and ceNaDC2) from
Caenorhabditis elegans and Their Relevance to Life
Span*
§,
, and
¶
Biochemistry and Molecular
Biology, and ¶ Obstetrics and Gynecology, Medical College of
Georgia, Augusta, Georgia 30912
*
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.
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