Abstract

Kidney water reabsorption is regulated by the hormone vasopressin (AVP) which exerts its effect on the water channel AQP2. AVP binds to its V2 receptors and causes, via elevation of cAMP, activation of protein kinase A (PKA) and phosphorylation of AQP2 at serine 256 (pS256), AQP2 translocation to the plasma membrane. Besides S256, in vivo AVP action co-incides with de-phosphoryation of S261, but the kinases involved are unknown. Bio-informatical analysis suggests that cdk1/5 may phosphorylate S261 and their potential relevance in AQP2 regulation was investigated. Immunohistochemistry and immunoblot analysis indicated that cdk1 and cdk5 are both expressed in renal principal cells. In ex-vivo kidney slices and MDCK-AQP2 cells, the cdk1/5 inhibitor roscovitine, increased pS256 and decreased pS261. In MDCK-AQP2 cells, immunocytochemistry and cell surface biotinylation showed that roscovitine caused AQP2 translocation to the apical membrane in the absence of forskolin, resulting in increased osmotic water permeability. However roscovitine did not affect PKA activity and cAMP levels. Interestingly roscovitive modulated the phosphorylation state of DARPP-32, a potent inhibitor of PP1 a phosphatase possibly involved in AQP2 de-phosphorylation. Together, these data indicate that cdks are functionally involved in the regulation of AQP2 trafficking and suggest that inhibition of cyclin kinases may be an alternative approach for treatment of Nephrogenic diabetes insipidus.

Autore Pugliese

• Valenti Giovanna , Tamma Grazia

Tutti gli autori

• VALENTI G.;TAMMA G.;SVELTO M.;RANIERI M.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2011

ISSN

1748-1708

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

Non Disponibile

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile