Phosphorylation of PACSIN2 at S313 Regulates Podocyte Architecture in Coordination with N-WASP
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 PACSI...
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MDPI AG
2023-05-01
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| author | Rim Bouslama Vincent Dumont Sonja Lindfors Lassi Paavolainen Jukka Tienari Harry Nisen Tuomas Mirtti Moin A. Saleem Daniel Gordin Per-Henrik Groop Shiro Suetsugu Sanna Lehtonen |
| author_facet | Rim Bouslama Vincent Dumont Sonja Lindfors Lassi Paavolainen Jukka Tienari Harry Nisen Tuomas Mirtti Moin A. Saleem Daniel Gordin Per-Henrik Groop Shiro Suetsugu Sanna Lehtonen |
| author_sort | Rim Bouslama |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T03:09:12Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T03:09:12Z |
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| series | Cells |
| spelling | doaj.art-051c46658c344b7d80aa86068b022ab42023-11-18T07:40:44ZengMDPI AGCells2073-44092023-05-011211148710.3390/cells12111487Phosphorylation of PACSIN2 at S313 Regulates Podocyte Architecture in Coordination with N-WASPRim Bouslama0Vincent Dumont1Sonja Lindfors2Lassi Paavolainen3Jukka Tienari4Harry Nisen5Tuomas Mirtti6Moin A. Saleem7Daniel Gordin8Per-Henrik Groop9Shiro Suetsugu10Sanna Lehtonen11Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, FinlandResearch Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, FinlandResearch Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, FinlandInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00290 Helsinki, FinlandDepartment of Pathology, University of Helsinki, Helsinki, and Helsinki University Hospital, 05850 Hyvinkää, FinlandDepartment of Urology, Helsinki University Hospital, 00029 HUS, FinlandDepartment of Pathology, Helsinki University Hospital, 00290 Helsinki, FinlandChildren’s Renal Unit, Bristol Medical School, University of Bristol, Bristol BS8 1TS, UKMinerva Foundation Institute for Medical Research, 00290 Helsinki, FinlandResearch Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, FinlandDivision of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma 630-0192, JapanResearch Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, FinlandChanges 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.https://www.mdpi.com/2073-4409/12/11/1487PACSIN2syndapin2actin cytoskeletonpodocytediabetic kidney diseaseFFA |
| spellingShingle | Rim Bouslama Vincent Dumont Sonja Lindfors Lassi Paavolainen Jukka Tienari Harry Nisen Tuomas Mirtti Moin A. Saleem Daniel Gordin Per-Henrik Groop Shiro Suetsugu Sanna Lehtonen Phosphorylation of PACSIN2 at S313 Regulates Podocyte Architecture in Coordination with N-WASP Cells PACSIN2 syndapin2 actin cytoskeleton podocyte diabetic kidney disease FFA |
| title | Phosphorylation of PACSIN2 at S313 Regulates Podocyte Architecture in Coordination with N-WASP |
| title_full | Phosphorylation of PACSIN2 at S313 Regulates Podocyte Architecture in Coordination with N-WASP |
| title_fullStr | Phosphorylation of PACSIN2 at S313 Regulates Podocyte Architecture in Coordination with N-WASP |
| title_full_unstemmed | Phosphorylation of PACSIN2 at S313 Regulates Podocyte Architecture in Coordination with N-WASP |
| title_short | Phosphorylation of PACSIN2 at S313 Regulates Podocyte Architecture in Coordination with N-WASP |
| title_sort | phosphorylation of pacsin2 at s313 regulates podocyte architecture in coordination with n wasp |
| topic | PACSIN2 syndapin2 actin cytoskeleton podocyte diabetic kidney disease FFA |
| url | https://www.mdpi.com/2073-4409/12/11/1487 |
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