A09 - Benzing & Schermer

A09 - Regulated cell death and kidney fibrosis as a consequence of mutation of cilia-associated genes

Thomas Benzing

Clinic II internal medicine, University of Cologne
Contact: thomas.benzing(at)uk-koeln.de
For more information visit: Nephrolab Cologne

Bernhard Schermer

Clinic II internal medicine, University of Cologne
Contact: bernhard.schermer(at)uk-koeln.de
For more information visit: Nephrolab Cologne

Abstract

Nephronophthisis (NPH) is an autosomal recessive disorder caused by mutations in single genes relevant for primary cilia, sensory organelles at the surface of tubular epithelial cells. The disease is characterised by progressive loss of renal tubular. However, the role of cell death and the molecular link to cilia signalling are still elusive. The aim of this project is to study the role of regulated cell death (RCD) in the pathogenesis of NPH and to elucidate the role of cilia and cilia-associated NPH proteins in controlling cell death signalling as well as the crosstalk of surrounding cells with dying kidney epithelial cells.

Recent Publications

Project A09 Publications 2020-2023

2022

Kieckhöfer, E., Slaats, G.G., Ebert, L.K., Albert, M.-C., Dafinger, C., Kashkar, H., Benzing, T. & Schermer, B. (2022) Primary cilia suppress Ripk3-mediated necroptosis. Cell Death Discovery 8, Article number: 477 (2022) https://doi.org/10.1038/s41420-022-01272-2

Kroef, V., Ruegenberg, S., Horn, M., Allmeroth, K., Ebert, L., Bozkus, S., Miethe, S., Elling, U., Schermer, B., Baumann, U., Denzel, M.S, (2022) GFPT2/GFAT2 and AMDHD2 act in tandem to control the hexosamine pathway. eLife 2022;11:e69223 doi: 10.7554/eLife.69223

Project related Publications

2003 - 2019

Benzing, T., and Schermer, B. (2011). Transition zone proteins and cilia dynamics. Nat Genet 43, 723-724.

Benzing, T., and Schermer, B. (2012). Clinical spectrum and pathogenesis of nephronophthisis. Curr Opin Nephrol Hypertens 21, 272-278.

Dafinger, C., Liebau, M.C., Elsayed, S.M., Hellenbroich, Y., Boltshauser, E., Korenke, G.C., Fabretti, F., Janecke, A.R., Ebermann, I., Nurnberg, G., …, Benzing, T., Schermer, B., and Bolz, H.J. (2011). Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and microtubule dynamics. J Clin Invest 121, 2662-2667.

Fliegauf, M., Benzing, T., and Omran, H. (2007). When cilia go bad: cilia defects and ciliopathies. Nat Rev Mol Cell Biol 8, 880-893.

Franke, M., Baessler, B., Vechtel, J., Dafinger, C., Hohne, M., Borgal, L., Gobel, H., Koerber, F., Maintz, D., Benzing, T., Schermer, B., and Persigehl, T. (2017). Magnetic resonance T2 mapping and diffusion-weighted imaging for early detection of cystogenesis and response to therapy in a mouse model of polycystic kidney disease. Kidney Int 92, 1544-1554.

Habbig, S., Bartram, M.P., Muller, R.U., Schwarz, R., Andriopoulos, N., Chen, S., Sagmuller, J.G., Hoehne, M., Burst, V., Liebau, M.C., Reinhardt, H.C., Benzing, T., and Schermer, B. (2011). NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway. J Cell Biol 193, 633-642.

Hildebrandt, F., Benzing, T., and Katsanis, N. (2011). Ciliopathies. N Engl J Med 364, 1533-1543.

Jain, M., Kaiser, R.W.J., Bohl, K., Hoehne, M., Gobel, H., Bartram, M.P., Habbig, S., Muller, R.U., Fogo, A.B., Benzing, T., Schermer, B., et al. (2019). Inactivation of Apoptosis Antagonizing Transcription Factor in tubular epithelial cells induces accumulation of DNA damage and nephronophthisis. Kidney Int 95, 846-858.

Kohli, P., Hohne, M., Jungst, C., Bertsch, S., Ebert, L.K., Schauss, A.C., Benzing, T., Rinschen, M.M., and Schermer, B. (2017). The ciliary membrane-associated proteome reveals actin-binding proteins as key components of cilia. EMBO Rep 18, 1521-1535.

Otto, E.A., Schermer, B., Obara, T., O'Toole, J.F., Hiller, K.S., Mueller, A.M., Ruf, R.G., Hoefele, J., Beekmann, F., Landau, D., ..., Benzing, T., and Hildebrandt, F. (2003). Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination. Nat Genet 34, 413-420.

UNIVERSITÄT ZU KÖLN

Sonderforschungsbereich 1403