Abstract
A cDNA coding for a Na+-dicarboxylate cotransporter, fNaDC-3, from winter flounder (Pseudopleuronectes americanus) kidney was isolated by functional expression in Xenopus laevis oocytes. The fNaDC-3 cDNA is 2384 nucleotides long and encodes a protein of 601 amino acids with a calculated molecular mass of 66.4 kDa. Secondary structure analysis predicts at least eight membrane-spanning domains. Transport of succinate by fNaDC-3 was sodium-dependent, could be inhibited by lithium, and evoked an inward current. The apparent affinity constant (Km) of fNaDC-3 for succinate of 30 microM resembles that of Na+-dicarboxylate transport in the basolateral membrane of mammalian renal proximal tubules. The substrates specific for the basolateral transporter, 2,3-dimethylsuccinate and cis-aconitate, not only inhibited succinate uptake but also evoked inward currents, proving that they are transported by fNaDC-3. Succinate transport via fNaDC-3 decreased by lowering pH, as did citrate transport, although much more moderately. These characteristics suggest that fNaDC-3 is a new type of Na+-dicarboxylate transporter that most likely corresponds to the Na+-dicarboxylate cotransporter in the basolateral membrane of mammalian renal proximal tubules.
Highlights
Krebs cycle intermediates represent important fuels for renal proximal tubule cells [1]
Succinate transport via fNaDC-3 decreased by lowering pH, as did citrate transport, much more moderately. These characteristics suggest that fNaDC-3 is a new type of Na؉-dicarboxylate transporter that most likely corresponds to the Na؉-dicarboxylate cotransporter in the basolateral membrane of mammalian renal proximal tubules
Uptake of citrate by the basolateral transporter was independent of pH [6] or slightly increased by raising pH from 5.5 to 7.0 [12], whereas citrate transport by the luminal transporter was much higher at lower pH than at neutral pH [6]
Summary
Krebs cycle intermediates represent important fuels for renal proximal tubule cells [1]. Transport of succinate by fNaDC-3 was sodium-dependent, could be inhibited by lithium, and evoked an inward current. The apparent affinity constant (Km) of fNaDC-3 for succinate of 30 M resembles that of Na؉-dicarboxylate transport in the basolateral membrane of mammalian renal proximal tubules.
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