Phosphorylation of PACSIN2 at S313 Regulates Podocyte Architecture in Coordination with N-WASP

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  • Rim Bouslama
    Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland
  • Vincent Dumont
    Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland
  • Sonja Lindfors
    Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland
  • Lassi Paavolainen
    Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00290 Helsinki, Finland
  • Jukka Tienari
    Department of Pathology, University of Helsinki, Helsinki, and Helsinki University Hospital, 05850 Hyvinkää, Finland
  • Harry Nisen
    Department of Urology, Helsinki University Hospital, 00029 HUS, Finland
  • Tuomas Mirtti
    Department of Pathology, Helsinki University Hospital, 00290 Helsinki, Finland
  • Moin A. Saleem
    Children’s Renal Unit, Bristol Medical School, University of Bristol, Bristol BS8 1TS, UK
  • Daniel Gordin
    Minerva Foundation Institute for Medical Research, 00290 Helsinki, Finland
  • Per-Henrik Groop
    Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland
  • Shiro Suetsugu
    Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma 630-0192, Japan
  • Sanna Lehtonen
    Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland

説明

<jats:p>Changes in the dynamic architecture of podocytes, the glomerular epithelial cells, lead to kidney dysfunction. Previous studies on protein kinase C and casein kinase 2 substrates in neurons 2 (PACSIN2), a known regulator of endocytosis and cytoskeletal organization, reveal a connection between PACSIN2 and kidney pathogenesis. Here, we show that the phosphorylation of PACSIN2 at serine 313 (S313) is increased in the glomeruli of rats with diabetic kidney disease. We found that phosphorylation at S313 is associated with kidney dysfunction and increased free fatty acids rather than with high glucose and diabetes alone. Phosphorylation of PACSIN2 emerged as a dynamic process that fine-tunes cell morphology and cytoskeletal arrangement, in cooperation with the regulator of the actin cytoskeleton, Neural Wiskott–Aldrich syndrome protein (N-WASP). PACSIN2 phosphorylation decreased N-WASP degradation while N-WASP inhibition triggered PACSIN2 phosphorylation at S313. Functionally, pS313-PACSIN2 regulated actin cytoskeleton rearrangement depending on the type of cell injury and the signaling pathways involved. Collectively, this study indicates that N-WASP induces phosphorylation of PACSIN2 at S313, which serves as a mechanism whereby cells regulate active actin-related processes. The dynamic phosphorylation of S313 is needed to regulate cytoskeletal reorganization.</jats:p>

収録刊行物

  • Cells

    Cells 12 (11), 1487-, 2023-05-27

    MDPI AG

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