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J. Biol. Chem., Vol. 277, Issue 28, 25728-25734, July 12, 2002

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Calcyclin Is an Early Vasopressin-induced Gene in the Renal Collecting Duct
ROLE IN THE LONG TERM REGULATION OF ION TRANSPORT^*

Nathalie Courtois-Coutry, Cathy Le Moellic, Sheerazad Boulkroun, Michel Fay, Françoise Cluzeaud, Brigitte Escoubet^§, Nicolette Farman, and Marcel Blot-Chabaud^¶

From INSERM  U478 and ^§ U426, Institut Fédératif de Recherches 02, Faculté de Médecine Xavier Bichat, Université Paris 7, 16 rue Henri Huchard, 75018 Paris, France

Long-term effects of arginine vasopressin (AVP) in the kidney involve the transcription of unidentified genes. By subtractive hybridization experiments performed on the RCCD₁ cortical collecting duct cell line, we identified calcyclin as an early AVP-induced gene (1 h). Calcyclin is a calcium-binding protein involved in the transduction of intracellular signals. In the kidney, calcyclin was localized at the mRNA level in the glomerulus, all along the collecting duct, and in the epithelium lining the papilla. In RCCD₁ cells and in m-IMCD₃ inner medullary collecting duct cells, calcyclin was evidenced in the cytoplasm. Calcyclin mRNA levels were progressively increased by AVP treatment in RCCD₁ (1.7-fold at 4 h) and m-IMCD₃ (2-fold at 7.5 h) cells. In RCCD₁ cells, calcyclin protein levels were increased by 4 h of AVP treatment. In vivo, treatment of genetically vasopressin-deficient Brattleboro rats with AVP for 4 days induced an increase in both calcyclin and aquaporin-2 mRNA expression. Finally, introduction of anti-calcyclin antibodies into RCCD₁ cells by permeabilizing the plasma membrane prevented the long-term (but not short-term) increase in short-circuit current induced by AVP. Taken together, these results suggest that calcyclin is an early vasopressin-induced gene that participates in the late phase of the hormone response in transepithelial ion transport.

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