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Compartmentalization of cAMP-dependent signaling by phosphodiesterase-4D is involved in the regulation of vasopressin-mediated water reabsorption in renal principal cells

Item Type:Article
Title:Compartmentalization of cAMP-dependent signaling by phosphodiesterase-4D is involved in the regulation of vasopressin-mediated water reabsorption in renal principal cells
Creators Name:Stefan, E. and Wiesner, B. and Baillie, G.S. and Mollajew, R. and Henn, V. and Lorenz, D. and Furkert, J. and Santamaria, K. and Nedvetsky, P.I. and Hundsrucker, C. and Beyermann, M. and Krause, E. and Pohl, P. and Gall, I. and MacIntyre, A.N. and Bachmann, S. and Houslay, M.D. and Rosenthal, W. and Klussmann, E.
Abstract:The cAMP/protein kinase A (PKA)-dependent insertion of water channel aquaporin-2 (AQP2)-bearing vesicles into the plasma membrane in renal collecting duct principal cells (AQP2 shuttle) constitutes the molecular basis of arginine vasopressin (AVP)-regulated water reabsorption. cAMP/PKA signaling systems are compartmentalized by A kinase anchoring proteins (AKAP) that tether PKA to subcellular sites and by phosphodiesterases (PDE) that terminate PKA signaling through hydrolysis of localized cAMP. In primary cultured principal cells, AVP causes focal activation of PKA. PKA and cAMP-specific phosphodiesterase-4D (PDE4D) are located on AQP2-bearing vesicles. The selective PDE4 inhibitor rolipram increases AKAP-tethered PKA activity on AQP2-bearing vesicles and enhances the AQP2 shuttle and thereby the osmotic water permeability. AKAP18delta, which is located on AQP2-bearing vesicles, directly interacts with PDE4D and PKA. In response to AVP, PDE4D and AQP2 translocate to the plasma membrane. Here PDE4D is activated through PKA phosphorylation and reduces the osmotic water permeability. Taken together, a novel, compartmentalized, and physiologically relevant cAMP-dependent signal transduction module on AQP2-bearing vesicles, comprising anchored PDE4D, AKAP18delta, and PKA, has been identified.
Keywords:3',5'-Cyclic-AMP Phosphodiesterases, Amino Acid Sequence, Amino Acid Sequence Homology, Aquaporin 2, Arginine Vasopressin, Biological Models, Collecting Kidney Tubules, Cultured Cells, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Molecular Sequence Data, Phosphodiesterase Inhibitors, Recombinant Proteins, Rolipram, Signal Transduction, Signal Transducing Adaptor Proteins, Type 3 Cyclic Nucleotide Phosphodiesterases, Type 4 Cyclic Nucleotide Phosphodiesterases, Water, Animals, Rats
Source:Journal of the American Society of Nephrology
ISSN:1046-6673
Publisher:American Society of Nephrology (U.S.A.)
Volume:18
Number:1
Page Range:199-212
Date:January 2007
Official Publication:https://doi.org/10.1681/ASN.2006020132
PubMed:View item in PubMed

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