Synphilin-1 regulates mechanotransduction in rigidity sensing through interaction with zyxin
Abstract Background Synphilin-1 has been studied extensively in the context of Parkinson’s disease pathology. However, the biophysical functions of synphilin-1 remain unexplored. To investigate its novel functionalities herein, cellular traction force and rigidity sensing ability are analyzed based...
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| Format: | Article |
| Language: | English |
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BMC
2025-05-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03429-4 |
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| author | Seok Gi Kim Jinyan Li Ji Su Hwang Muhammad Anwar Ul Hassan Ye Eun Sim Ju Yeon Lee Jung-Soon Mo Myeong Ok Kim Gwang Lee Sungsu Park |
| author_facet | Seok Gi Kim Jinyan Li Ji Su Hwang Muhammad Anwar Ul Hassan Ye Eun Sim Ju Yeon Lee Jung-Soon Mo Myeong Ok Kim Gwang Lee Sungsu Park |
| author_sort | Seok Gi Kim |
| collection | DOAJ |
| description | Abstract Background Synphilin-1 has been studied extensively in the context of Parkinson’s disease pathology. However, the biophysical functions of synphilin-1 remain unexplored. To investigate its novel functionalities herein, cellular traction force and rigidity sensing ability are analyzed based on synphilin-1 overexpression using elastomeric pillar arrays and substrates of varying stiffness. Molecular changes are analyzed using RNA sequencing-based transcriptomic and liquid chromatography-tandem mass spectrometry-based proteomic analyses. Results Synphilin-1 overexpression reduces cell area, with a decline of local contraction on elastomeric pillar arrays. Cells overexpressing synphilin-1 exhibit an impaired ability to respond to substrate rigidity; however, synphilin-1 knockdown restores rigidity sensing abilities. Integrated omics analysis and in silico prediction corroborate the phenotypic alterations induced by synphilin-1 overexpression at a biophysical level. Zyxin emerges as a novel synphilin-1 binding protein, and synphilin-1 overexpression reduces the nuclear translocation of yes-associated protein. Conclusion These findings provide novel insights into the biophysical functions of synphilin-1, suggesting a potential protective role to the altered extracellular matrix, which may be relevant to neurodegenerative conditions such as Parkinson’s disease. Graphical Abstract |
| format | Article |
| id | doaj-art-46c33505319b40d99997da8daaba0112 |
| institution | DOAJ |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-46c33505319b40d99997da8daaba01122025-08-20T03:07:54ZengBMCJournal of Nanobiotechnology1477-31552025-05-0123112010.1186/s12951-025-03429-4Synphilin-1 regulates mechanotransduction in rigidity sensing through interaction with zyxinSeok Gi Kim0Jinyan Li1Ji Su Hwang2Muhammad Anwar Ul Hassan3Ye Eun Sim4Ju Yeon Lee5Jung-Soon Mo6Myeong Ok Kim7Gwang Lee8Sungsu Park9Department of Molecular Science and Technology, Ajou UniversityDepartment of Mechanical Engineering, Sungkyunkwan UniversityDepartment of Molecular Science and Technology, Ajou UniversityDepartment of Mechanical Engineering, Sungkyunkwan UniversityDepartment of Biomedical Sciences, Graduate School, Ajou University School of MedicineDigital Omics Research Center, Korea Basic Science InstituteDepartment of Biomedical Sciences, Graduate School, Ajou University School of MedicineDivision of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National UniversityDepartment of Molecular Science and Technology, Ajou UniversityDepartment of Mechanical Engineering, Sungkyunkwan UniversityAbstract Background Synphilin-1 has been studied extensively in the context of Parkinson’s disease pathology. However, the biophysical functions of synphilin-1 remain unexplored. To investigate its novel functionalities herein, cellular traction force and rigidity sensing ability are analyzed based on synphilin-1 overexpression using elastomeric pillar arrays and substrates of varying stiffness. Molecular changes are analyzed using RNA sequencing-based transcriptomic and liquid chromatography-tandem mass spectrometry-based proteomic analyses. Results Synphilin-1 overexpression reduces cell area, with a decline of local contraction on elastomeric pillar arrays. Cells overexpressing synphilin-1 exhibit an impaired ability to respond to substrate rigidity; however, synphilin-1 knockdown restores rigidity sensing abilities. Integrated omics analysis and in silico prediction corroborate the phenotypic alterations induced by synphilin-1 overexpression at a biophysical level. Zyxin emerges as a novel synphilin-1 binding protein, and synphilin-1 overexpression reduces the nuclear translocation of yes-associated protein. Conclusion These findings provide novel insights into the biophysical functions of synphilin-1, suggesting a potential protective role to the altered extracellular matrix, which may be relevant to neurodegenerative conditions such as Parkinson’s disease. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03429-4MechanobiologyMulti-omicsRigidity sensingSynphilin-1Zyxin |
| spellingShingle | Seok Gi Kim Jinyan Li Ji Su Hwang Muhammad Anwar Ul Hassan Ye Eun Sim Ju Yeon Lee Jung-Soon Mo Myeong Ok Kim Gwang Lee Sungsu Park Synphilin-1 regulates mechanotransduction in rigidity sensing through interaction with zyxin Journal of Nanobiotechnology Mechanobiology Multi-omics Rigidity sensing Synphilin-1 Zyxin |
| title | Synphilin-1 regulates mechanotransduction in rigidity sensing through interaction with zyxin |
| title_full | Synphilin-1 regulates mechanotransduction in rigidity sensing through interaction with zyxin |
| title_fullStr | Synphilin-1 regulates mechanotransduction in rigidity sensing through interaction with zyxin |
| title_full_unstemmed | Synphilin-1 regulates mechanotransduction in rigidity sensing through interaction with zyxin |
| title_short | Synphilin-1 regulates mechanotransduction in rigidity sensing through interaction with zyxin |
| title_sort | synphilin 1 regulates mechanotransduction in rigidity sensing through interaction with zyxin |
| topic | Mechanobiology Multi-omics Rigidity sensing Synphilin-1 Zyxin |
| url | https://doi.org/10.1186/s12951-025-03429-4 |
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