The role of calcium mediated actin rearrangement (CaAR) in podocyte function

    We have identified a fundamental ability of mammalian cells to reset their actin cytoskeleton in response to calcium influx (Calcium mediated Actin Rearrangement - CaAR). Calcium, actin and a key regulator of CaAR, the formin INF2, have been implicated in injury of podocytes, the cells responsible for ultrafiltration in the kidney. In this proposal we therefore want to establish the molecular basis and physiological relevance of CaAR for the function of podocytes. We will use a combination of live cell imaging and genetic perturbations in cultured cells and mouse models, with a particular focus on the role and biochemical interactions of INF2.

    Research area: Cell biology, clinical nephrology

    Prof. Dr. Roland Wedlich-Söldner
    Prof. Dr. Hermann Pavenstädt

    Funding period: July 2016 - June 2020

    • Publications

      Original articles

      • Dlugos CP, Picciotto C, Lepa C, Krakow M, Stöber A, Eddy ML, Weide T, Jeibmann A, P Krahn M, Van Marck V, Klingauf J, Ricker A, Wedlich-Söldner R, Pavenstädt H, Klämbt C, George B (2019) Nephrin Signaling Results in Integrin beta1 Activation. JASN 30: 1006-1019.
      • Bonse J, Wennmann DO, Kremerskothen J, Weide T, Michgehl U, Pavenstädt H, Vollenbröker B. (2018) Nuclear YAP localization as a key regulator of podocyte function. Cell Death Dis 9:850.
      • Prystopiuk V, Fels B, Simon CS, Liashkovich I, Pasrednik D, Kronlage C, Wedlich-Söldner R, Oberleithner H, Fels J. (2018) A two-phase response of endothelial cells to hydrostatic pressure. J Cell Sci 131: e99473.
      • Granado D, Müller D, Krausel V, Kruzel-Davila E, Schuberth C, Eschborn M, Wedlich-Söldner R, Skorecki K, Pavenstädt H, Michgehl U, Weide T (2017). Intracellular APOL1 Risk Variants Cause Cytotoxicity Accompanied by Energy Depletion. Journal of the American Society of Nephrology, 28(11), 3227-3238. (doi: 10.1681/ASN.2016111220)
      • Horsthemke M, Bachg AC, Groll K, Moyzio S, Müther B, Hemkemeyer SA, Wedlich-Söldner R, Sixt M, Tacke S, Bähler M, Hanley PJ (2017) Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion. JBC 292: 7258-7273.
      • Wales P, Schuberth C E, Aufschnaiter R, Fels J, García-Aguilar I, Janning A, Kuhlmann J, …, Pavenstädt H, Vogl T, Roth J, Wedlich-Söldner R (2016). Calcium-mediated actin reset (CaAR) mediates acute cell adaptations. Elife, 5.  (doi: 10.7554/eLife.19850)