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Synthesis, maturation, and trafficking of human Na+-dicarboxylate cotransporter NaDC1 requires the chaperone activity of cyclophilin B.
Bergeron MJ
,
Bürzle M
,
Kovacs G
,
Simonin A
,
Hediger MA
.
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Renal excretion of citrate, an inhibitor of calcium stone formation, is controlled mainly by reabsorption via the apical Na(+)-dicarboxylate cotransporter NaDC1 (SLC13A2) in the proximal tubule. Recently, it has been shown that the protein phosphatase calcineurin inhibitors cyclosporin A (CsA) and FK-506 induce hypocitraturia, a risk factor for nephrolithiasis in kidney transplant patients, but apparently through urine acidification. This suggests that these agents up-regulate NaDC1 activity. Using the Xenopus lævis oocyte and HEK293 cell expression systems, we examined first the effect of both anti-calcineurins on NaDC1 activity and expression. While FK-506 had no effect, CsA reduced NaDC1-mediated citrate transport by lowering heterologous carrier expression (as well as endogenous carrier expression in HEK293 cells), indicating that calcineurin is not involved. Given that CsA also binds specifically to cyclophilins, we determined next whether such proteins could account for the observed changes by examining the effect of selected cyclophilin wild types and mutants on NaDC1 activity and cyclophilin-specific siRNA. Interestingly, our data show that the cyclophilin isoform B is likely responsible for down-regulation of carrier expression by CsA and that it does so via its chaperone activity on NaDC1 (by direct interaction) rather than its rotamase activity. We have thus identified for the first time a regulatory partner for NaDC1, and have gained novel mechanistic insight into the effect of CsA on renal citrate transport and kidney stone disease, as well as into the regulation of membrane transporters in general.
Aruga,
Chronic metabolic acidosis increases NaDC-1 mRNA and protein abundance in rat kidney.
2000, Pubmed
Aruga,
Chronic metabolic acidosis increases NaDC-1 mRNA and protein abundance in rat kidney.
2000,
Pubmed
Baker,
The cyclophilin homolog NinaA functions as a chaperone, forming a stable complex in vivo with its protein target rhodopsin.
1994,
Pubmed
Bollo,
Calcineurin interacts with PERK and dephosphorylates calnexin to relieve ER stress in mammals and frogs.
2010,
Pubmed
,
Xenbase
Bouvier,
Cyclosporine triggers endoplasmic reticulum stress in endothelial cells: a role for endothelial phenotypic changes and death.
2009,
Pubmed
Chen,
Cyclosporin A selectively reduces the functional expression of Kir2.1 potassium channels in Xenopus oocytes.
1998,
Pubmed
,
Xenbase
Colley,
The cyclophilin homolog ninaA is required in the secretory pathway.
1991,
Pubmed
Elbaz,
Modulation of Na+-Ca2+ exchanger expression by immunosuppressive drugs is isoform-specific.
2008,
Pubmed
Fujiwara,
The effects of immunosuppressants on FAS-mediated activation-induced cell death in human T lymphocytes.
2003,
Pubmed
Galat,
Peptidylprolyl cis/trans isomerases (immunophilins): biological diversity--targets--functions.
2003,
Pubmed
Hamm,
Renal handling of citrate.
1990,
Pubmed
Hamm,
Pathophysiology of hypocitraturic nephrolithiasis.
2002,
Pubmed
He,
Sodium dicarboxylate cotransporter-1 expression in renal tissues and its role in rat experimental nephrolithiasis.
2004,
Pubmed
Heering,
Tubular dysfunction following kidney transplantation.
1996,
Pubmed
Helekar,
Peptidyl prolyl cis-trans isomerase activity of cyclophilin A in functional homo-oligomeric receptor expression.
1997,
Pubmed
,
Xenbase
Ho,
Generation and characterization of sodium-dicarboxylate cotransporter-deficient mice.
2007,
Pubmed
Hong,
Transgenic mice overexpressing cyclophilin A are resistant to cyclosporin A-induced nephrotoxicity via peptidyl-prolyl cis-trans isomerase activity.
2004,
Pubmed
Jenkins,
Transport of citrate across renal brush border membrane: effects of dietary acid and alkali loading.
1985,
Pubmed
Keven,
Renal tubular acidosis after kidney transplantation--incidence, risk factors and clinical implications.
2007,
Pubmed
Kimchi-Sarfaty,
Transport activity and surface expression of the Na+-Ca2+ exchanger NCX1 are inhibited by the immunosuppressive agent cyclosporin A and by the nonimmunosuppressive agent PSC833.
2002,
Pubmed
Kino,
FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro.
1987,
Pubmed
Long,
Structure-activity relationship studies of salubrinal lead to its active biotinylated derivative.
2005,
Pubmed
Mochida,
Calcineurin is required to release Xenopus egg extracts from meiotic M phase.
2007,
Pubmed
,
Xenbase
Okamoto,
Associations between renal sodium-citrate cotransporter (hNaDC-1) gene polymorphism and urinary citrate excretion in recurrent renal calcium stone formers and normal controls.
2007,
Pubmed
Pajor,
Molecular cloning and functional expression of a sodium-dicarboxylate cotransporter from human kidney.
1996,
Pubmed
,
Xenbase
Pallet,
Cyclosporine-induced endoplasmic reticulum stress triggers tubular phenotypic changes and death.
2008,
Pubmed
Price,
Cyclophilin B trafficking through the secretory pathway is altered by binding of cyclosporin A.
1994,
Pubmed
Price,
Human cyclophilin B: a second cyclophilin gene encodes a peptidyl-prolyl isomerase with a signal sequence.
1991,
Pubmed
Romero,
Expression cloning using Xenopus laevis oocytes.
1998,
Pubmed
,
Xenbase
Rosado,
SERCA2b activity is regulated by cyclophilins in human platelets.
2010,
Pubmed
Rycyzyn,
The intranuclear prolactin/cyclophilin B complex as a transcriptional inducer.
2002,
Pubmed
Shaw,
Canadian Consensus Meeting on cyclosporine monitoring: report of the consensus panel.
1990,
Pubmed
Shiraishi,
Post-translational reduction of cell surface expression of insulin receptors by cyclosporin A, FK506 and rapamycin in bovine adrenal chromaffin cells.
2000,
Pubmed
Stapenhorst,
Hypocitraturia as a risk factor for nephrocalcinosis after kidney transplantation.
2005,
Pubmed
Stumpf,
The human TRPV6 channel protein is associated with cyclophilin B in human placenta.
2008,
Pubmed
,
Xenbase
Suñé,
Cyclophilin B interacts with sodium-potassium ATPase and is required for pump activity in proximal tubule cells of the kidney.
2010,
Pubmed
Tegzess,
Prospective serial renal function studies in patients with nonrenal disease treated with cyclosporine A.
1988,
Pubmed
Tran,
Cyclosporin A inhibits creatine uptake by altering surface expression of the creatine transporter.
2000,
Pubmed
,
Xenbase
Tran,
Inhibition of taurine transport by cyclosporin A is due to altered surface abundance of the taurine transporter and is reversible.
2009,
Pubmed
Wagner,
The use of Xenopus laevis oocytes for the functional characterization of heterologously expressed membrane proteins.
2000,
Pubmed
,
Xenbase
Watanabe,
Cyclosporin A produces distal renal tubular acidosis by blocking peptidyl prolyl cis-trans isomerase activity of cyclophilin.
2005,
Pubmed
Wek,
Translational control and the unfolded protein response.
2007,
Pubmed
Yurchenko,
Regulation of CD147 cell surface expression: involvement of the proline residue in the CD147 transmembrane domain.
2005,
Pubmed
