Identification of proteins controlling AVP-mediated water reabsorption Jana Bogum, Dörte Faust, Andrey C.C. Goncalves, Aline Kirschner Only a few proteins and stimuli are known to regulate the localisation of AQP2. A major goal of our group is to gain mechanistic insight into the molecular mechanisms controlling AVP-mediated water reabsorption by identifying new players that participate in the control of AQP2. Such new players may also be involved in other cAMP/PKA-controlled exocytic processes such as renin secretion from juxtaglomerular cells in the kidney.
Patent applications Klußmann E, Schäfer, G. Milic, J., Rosenthal, W. Schillinger, C., Krause, G., Rademann, J. Peptidomimetika zur Hemmung von AKAP-PKAInteraktionen als Arzneistoffe. EP11168008.8. Klußmann E, Milic, J., Bergmann, M., Rosenthal, W. Arylaminomethylenbenzothiophenone als Arzneimittel. 2011011818380200DE.
The C-terminal tail of AQP2 contains a phosphorylation site at S261 (pS261), which is phosphorylated under resting conditions (Fig. 2). The phosphorylation decreases in response to V2R stimulation in cultured principal cells. Recently, we have shown that p38 mitogen-activated protein kinase (MAPK) is one of the kinases controlling the phosphorylation of S261. The AVP-dependent decrease of pS261 is associated with a reduction in p38 MAPK activity, a decrease in poly-ubiquitination of AQP2 and reduced proteasomal degradation. This increases AQP2 abundance. This novel regulatory mechanism of AQP2 abundance is likely to play a role in rapidly increasing water reabsorption by the renal collecting duct in response to AVP. Selected Publications Christian, F, Szaszák, M, Drewianka, S, Friedl, S, Lorenz, D, Furkert, J, Vargas, C, Schmieder, P, Götz, F, Göttert, H, Joshi, M, Reif, B, Haase, H, Morano, I, Kass, R, Hampel, K, Kashin, D, Genieser, H-G, Herberg, FW, Willoughby, D, Cooper, DMF, Baillie, GS, Houslay, MD, v. Kries, JP, Zimmermann, B, Rosenthal, W, Klussmann, E. (2011). Small molecule AKAP/PKA interaction disruptors that activate PKA increase cardiac contractility. J. Biol. Chem. 286, 9079–9096. Nedvetsky, PI, Tabor, V, Tamma, G, Beulshausen, S, Mutig, K, Boltzen, M, Petrucci, O, Vossenkämper, A, Wiesner, B, Bachmann, S, Rosenthal, W, Klussmann, E. (2010). Protein kinase A and p38 MAP Kinase crosstalk regulates the abundance of aquaporin-2 in renal principal cells at the post-translational level. J. Am. Soc. Nephrol. 21, 1645-56. Hundsrucker, C, Skroblin, P, Christian, F, Zenn, M, Popara, V, Joshi, M, Herberg, FW, Reif, B, Rosenthal, W, Klussmann, E (2010). The domain of unknown function (DUF) 727 of glycogen synthase kinase interaction protein (GSKIP) facilitates anchoring of protein kinase A. J. Biol. Chem. 285, 5507–5521. Lygren, B, Carlson, C, Santamaria, K, Lissandron, V, McSorley, T, Litzenberg, J, Lorenz, D, Wiesner, B, Rosenthal, W, Zaccolo, M, Tasken, K, Klussmann, E. (2007) AKAP complex regulates Ca2+ re-uptake into heart sarcoplasmic reticulum. EMBO. Rep. 8, 1061-1067. Stefan, E, Wiesner, B, Baillie, GS, Mollajew, R, Henn, V, Lorenz, D, Furkert, J, Santamaria, K, Nedvetsky, P, Hundsrucker, C, Beyermann, M, Krause, E, Pohl, P, Gall, I, MacIntyre, AN, Bachmann, S, Houslay, MD, Rosenthal, W, and Klussmann, E. (2007) Compartmentalization of cAMP-dependent signaling by phosphodiesterase-4D is involved in the regulation of vasopressin-mediated water reabsorption in renal principal cells. J. Am. Soc. Nephrol. 1, 199-212.
Structure of the Group Group Leaders Prof. Dr. Walter Rosenthal PD Dr. Enno Klußmann Scientists Dr. Adeeb El-Dahshan (externally funded) Dr. Andrey da Costa Goncalves (externally funded) Dr. Frank Götz (externally funded) Dr. Jelena Milic Dr. Marie Christine Moutty (externally funded) Dr. Kerstin Zühlke (externally funded) Graduate Students Philipp Skroblin (part time; externally funded)
Gesa Schäfer (part time; externally funded) Jana Bogum (part time; externally funded) Dörte Faust (part time) Jessica Tröger (part time) Technical Assistance Beate Eisermann (externally funded) Andrea Geelhaar Silvia Niquet (externally funded) Aline Kirschner Vivian Schultz (1st year apprentice) Secretariat Shirley-Ann Jennifer Felsenberg
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