Protein kinase C-mediated regulation of the renal Na(+)/dicarboxylate cotransporter, NaDC-1

Biochim Biophys Acta. 1999 Aug 20;1420(1-2):223-30. doi: 10.1016/s0005-2736(99)00102-9.


The Na(+)/dicarboxylate cotransporter of the renal proximal tubule, NaDC-1, reabsorbs Krebs cycle intermediates, such as succinate and citrate, from the tubular filtrate. Although long-term regulation of this transporter by chronic metabolic acidosis and K(+) deficiency is well documented, there is no information on acute regulation of NaDC-1. In the present study, the transport of succinate in Xenopus oocytes expressing NaDC-1 was inhibited up to 95% by two activators of protein kinase C, phorbol 12-myristate, 13-acetate (PMA) and sn-1, 2-dioctanoylglycerol (DOG). Activation of protein kinase A had no effect on NaDC-1 activity. The inhibition of NaDC-1 transport by PMA was dose-dependent, and could be prevented by incubation of the oocytes with staurosporine. Mutations of the two consensus protein kinase C phosphorylation sites in NaDC-1 did not affect inhibition by PMA. The inhibitory effects of PMA were partially prevented by cytochalasin D, which disrupts microfilaments and endocytosis. PMA treatment was also associated with a decrease of approximately 30% in the amount of NaDC-1 protein found on the plasma membrane. We conclude that the inhibition of NaDC-1 transport activity by PMA occurs by a combination of endocytosis and inhibition of transport activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Colchicine / pharmacology
  • Cytochalasin D / pharmacology
  • DNA Primers / genetics
  • Dicarboxylic Acid Transporters*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Female
  • In Vitro Techniques
  • Kidney Tubules, Proximal / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mutagenesis, Site-Directed
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Organic Anion Transporters, Sodium-Dependent*
  • Protein Kinase C / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Symporters*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Xenopus laevis


  • Carrier Proteins
  • DNA Primers
  • Dicarboxylic Acid Transporters
  • Enzyme Inhibitors
  • Membrane Proteins
  • Organic Anion Transporters, Sodium-Dependent
  • Recombinant Proteins
  • SLC13A2 protein, human
  • Symporters
  • Cytochalasin D
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate
  • Colchicine