Calcium mediated actin rearrangement (CAR) in podocyte development and pathogenesis

    We have characterized a large panel of mutants in the calcium-regulated actin nucleator inverted formin 2 (INF2) that cause the kidney disease “focal segmental glomerulosclerosis” (FSGS) and the neurological disorder Charcot Marie Tooth disease (CMT). While all CMT linked INF2 mutations result in complete activation of the formin, many FSGS-linked mutations mediate partial INF2 activation. We will now characterize the actin regulatory network in podocytes during recovery from plasma membrane damage and characterize the consequences of INF2 deletion in mice on glomerular morphology, function and repair.

    Research area: Cell biology, clinical nephrology

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

    Funding period: July 2016 - June 2024

    • Publications

      Original articles

      • Bayraktar S, Nehrig J, Menis E, Karli K, Janning A, Struk T, Halbritter J, Michgehl U, Krahn MP, Schuberth CE, Pavenstädt H, Wedlich-Söldner R (2020) A Deregulated Stress Response Underlies Distinct INF2-Associated Disease Profiles. J Am Soc Nephrol 31(6):1296-1313
      • Skryabin BV, Kummerfeld DM, Gubar L, Seeger B, Kaiser H, Stegemann A, Roth J, Meuth SG, Pavenstädt H, Sherwood J, Pap T, Wedlich-Söldner R, Sunderkötter C, Schwartz YB, Brosius J, Rozhdestvensky TS (2020) Pervasive head-to-tail insertions of DNA templates mask desired CRISPR-Cas9-mediated genome editing events. Sci Adv. 6(7):eaax2941

      • 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)