PUBLICATION

Zebrafish Slc5a12 encodes an electroneutral sodium monocarboxylate transporter (SMCTn): A comparison to the electrogenic SMCT (SMCTe/Slc5a8)

Authors
Plata, C., Sussman, C.R., Sindic, A., Liang, J.O., Mount, D.B., Josephs, Z.M., Chang, M.H., and Romero, M.F.
ID
ZDB-PUB-070210-36
Date
2007
Source
The Journal of biological chemistry   282(16): 11996-12009 (Journal)
Registered Authors
Liang, Jennifer, Sussman, Caroline R.
Keywords
none
MeSH Terms
  • Animals
  • Cation Transport Proteins/physiology*
  • Electrophysiology
  • Humans
  • Kidney/metabolism
  • Kinetics
  • Models, Biological
  • Molecular Sequence Data
  • Monocarboxylic Acid Transporters/genetics
  • Monocarboxylic Acid Transporters/physiology*
  • Neurons/metabolism
  • Oocytes/metabolism
  • Sodium/metabolism*
  • Symporters
  • Tissue Distribution
  • Xenopus
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed
17255103 Full text @ J. Biol. Chem.
Abstract
We have identified and characterized two different sodium-coupled monocarboxylate cotransporters (SMCT) from zebrafish (Danio rerio): electrogenic (zSMCTe) and electroneutral (zSMCTn). zSMCTn is the 12th member of zebrafish Slc5 gene family (zSlc5a12). Both zSMCT sequences have ~50% homology to human SLC5A8 (hSMCT). Transport function and kinetics were measured in Xenopus oocytes injected with zSMCT cRNAs by measurement of intracellular Na+ activity ([Na+]i) and membrane potential. Both zSMCTs-oocytes increased [Na+]i with addition of monocarboxylates (MC), such as lactate, pyruvate, nicotinate and butyrate. Using two electrode voltage clamp experiments, we measured currents elicited from zSMCTe after MC addition. MC-elicited currents from zSMCTe were similar to hSMCT currents. In contrast, we found no significant MC-elicited current in either zSMCTn or control-oocytes. Kinetic data show that zSMCTe has a higher affinity for lactate, nicotinate and pyruvate (KmL lactate = 0.17 0.02 mM, Kmnicotinate = 0.54 0.12 mM @ 150mV) than zSMCTn (KmL lactate =1.81 0.19 mM, Kmnicotinate = 23.68 +/- 4.88mM). In situ hybridization showed that both zSMCTs are expressed in 1, 3 and 5 day old zebrafish embryos. Both zSMCTs are abundantly expressed in the brain, eyes, intestine and kidney. Within the kidney, zSMCTn mRNA is expressed in pronephric tubules whereas zSMCTe mRNA is more distal in pronephric ducts. zSMCTn is expressed in exocrine pancreas but zSMCTe is not. Roles for Na+ coupled monocarboxylate cotransporters have not been described for the brain or eye. In summary, zSMCTe is the zebrafish SLC5A8 ortholog and zSMCTn is a novel, electroneutral SMCT (zSlc5a12). Slc5a12 in higher vertebrates is likely responsible for the electroneutral Na+/lactate cotransport reported in mammalian and amphibian kidneys.
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