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J. Nanobiotechnol., 14 May 2025 | https://doi.org/10.1186/s12951-025-03429-4
Synphilin-1 regulates mechanotransduction in rigidity sensing through interaction with zyxin
Seok Gi Kim1†, Jinyan Li2†, Ji Su Hwang1†, Muhammad Anwar Ul Hassan2, Ye Eun Sim3, Ju Yeon Lee4, Jung-Soon Mo3,5, Myeong Ok Kim6, Gwang Lee1,7* and Sungsu Park2,8,9*
1Department of Molecular Science and Technology, Ajou University, 206 World cup-ro, Suwon 16499, Republic of Korea
2Department of Mechanical Engineering, Sungkyunkwan University, 2066 Seobu-ro, Suwon 16419, Republic of Korea
3Department of Biomedical Sciences, Graduate School, Ajou University School of Medicine, 164 World cup-ro, Suwon 16499, Republic of Korea
4Digital Omics Research Center, Korea Basic Science Institute, 162 Yeongudanji-ro, Cheongju 28119, Republic of Korea
5Institute of Medical Science, Ajou University School of Medicine, 164 World cup-ro, Suwon 16499, Republic of Korea
6Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea
7Department of Physiology, Ajou University School of Medicine, 164 World Cup-ro, Suwon 16499, Republic of Korea
8Institute of Quantum Biophysics (IQB), Sungkyunkwan University, 2066 Seobu-ro, Suwon 16419, Republic of Korea
9Department of MetaBioHealth, Sungkyunkwan University, 2066 Seoburo, Suwon 16419, Republic of Korea
†Seok Gi Kim, Jinyan Li and Ji Su Hwang contributed equally to this work.
*Correspondence: Gwang Lee, Sungsu Park
1Department of Molecular Science and Technology, Ajou University, 206 World cup-ro, Suwon 16499, Republic of Korea
2Department of Mechanical Engineering, Sungkyunkwan University, 2066 Seobu-ro, Suwon 16419, Republic of Korea
3Department of Biomedical Sciences, Graduate School, Ajou University School of Medicine, 164 World cup-ro, Suwon 16499, Republic of Korea
4Digital Omics Research Center, Korea Basic Science Institute, 162 Yeongudanji-ro, Cheongju 28119, Republic of Korea
5Institute of Medical Science, Ajou University School of Medicine, 164 World cup-ro, Suwon 16499, Republic of Korea
6Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea
7Department of Physiology, Ajou University School of Medicine, 164 World Cup-ro, Suwon 16499, Republic of Korea
8Institute of Quantum Biophysics (IQB), Sungkyunkwan University, 2066 Seobu-ro, Suwon 16419, Republic of Korea
9Department of MetaBioHealth, Sungkyunkwan University, 2066 Seoburo, Suwon 16419, Republic of Korea
†Seok Gi Kim, Jinyan Li and Ji Su Hwang contributed equally to this work.
*Correspondence: Gwang Lee, Sungsu Park
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.
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.
논문정보
- Research article
- 2025년 05월 (BRIC 등록일 2025-05-15)
- 국내 연구진
- 생명과학 > 신경생물학
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