PRAG1 Condensation Drives Cell Contraction Under Stress
Peak1-related, kinase-activating pseudokinase 1 (PRAG1), a member of the pseudopodium-enriched atypical kinase (PEAK) family of pseudokinases, has been reported to play a role in regulating cell morphology. However, the molecular mechanism for this function remains elusive. In this study, we demonst...
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MDPI AG
2025-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/15/3/379 |
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| author | Peiwu Ye Peiran Jiang Luyu Ye Min Liu Qiuyuan Fang Peilin Yu Jianhong Luo Huanxing Su Wei Yang |
| author_facet | Peiwu Ye Peiran Jiang Luyu Ye Min Liu Qiuyuan Fang Peilin Yu Jianhong Luo Huanxing Su Wei Yang |
| author_sort | Peiwu Ye |
| collection | DOAJ |
| description | Peak1-related, kinase-activating pseudokinase 1 (PRAG1), a member of the pseudopodium-enriched atypical kinase (PEAK) family of pseudokinases, has been reported to play a role in regulating cell morphology. However, the molecular mechanism for this function remains elusive. In this study, we demonstrate that PRAG1 forms dynamic condensates in cells mediated by its αN and αJ helices. Importantly, we found that PRAG1 condensates functioned in mediating cell contraction, while condensate-formation-deficient PRAG1 mutants lost this function. Remarkably, the formation of spherical PRAG1 condensates appears to be a common phenomenon in diverse stress models, as well as in dopaminergic (DA) neurons derived from a Parkinson’s disease patient. Our findings reveal a novel mechanism through which PRAG1 drives cell contraction and suggest a potential link between aberrant PRAG1 phase separation and stress-induced cell contraction. PRAG1 condensation drives cell contraction under stress. |
| format | Article |
| id | doaj-art-5ee33746b08641aeb6c134b8ae07c72c |
| institution | OA Journals |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-5ee33746b08641aeb6c134b8ae07c72c2025-08-20T02:11:22ZengMDPI AGBiomolecules2218-273X2025-03-0115337910.3390/biom15030379PRAG1 Condensation Drives Cell Contraction Under StressPeiwu Ye0Peiran Jiang1Luyu Ye2Min Liu3Qiuyuan Fang4Peilin Yu5Jianhong Luo6Huanxing Su7Wei Yang8Institute of Chinese Medical Sciences, University of Macau, Macau 999078, ChinaDepartment of Neurosurgery of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Biophysics, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Biophysics, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Biophysics, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Toxicology, School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, ChinaSchool of Brain Science and Brain Medicine, Zhejiang University, Hangzhou 310058, ChinaInstitute of Chinese Medical Sciences, University of Macau, Macau 999078, ChinaDepartment of Neurosurgery of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, ChinaPeak1-related, kinase-activating pseudokinase 1 (PRAG1), a member of the pseudopodium-enriched atypical kinase (PEAK) family of pseudokinases, has been reported to play a role in regulating cell morphology. However, the molecular mechanism for this function remains elusive. In this study, we demonstrate that PRAG1 forms dynamic condensates in cells mediated by its αN and αJ helices. Importantly, we found that PRAG1 condensates functioned in mediating cell contraction, while condensate-formation-deficient PRAG1 mutants lost this function. Remarkably, the formation of spherical PRAG1 condensates appears to be a common phenomenon in diverse stress models, as well as in dopaminergic (DA) neurons derived from a Parkinson’s disease patient. Our findings reveal a novel mechanism through which PRAG1 drives cell contraction and suggest a potential link between aberrant PRAG1 phase separation and stress-induced cell contraction. PRAG1 condensation drives cell contraction under stress.https://www.mdpi.com/2218-273X/15/3/379PRAG1condensationphase separationcell contractionstress |
| spellingShingle | Peiwu Ye Peiran Jiang Luyu Ye Min Liu Qiuyuan Fang Peilin Yu Jianhong Luo Huanxing Su Wei Yang PRAG1 Condensation Drives Cell Contraction Under Stress Biomolecules PRAG1 condensation phase separation cell contraction stress |
| title | PRAG1 Condensation Drives Cell Contraction Under Stress |
| title_full | PRAG1 Condensation Drives Cell Contraction Under Stress |
| title_fullStr | PRAG1 Condensation Drives Cell Contraction Under Stress |
| title_full_unstemmed | PRAG1 Condensation Drives Cell Contraction Under Stress |
| title_short | PRAG1 Condensation Drives Cell Contraction Under Stress |
| title_sort | prag1 condensation drives cell contraction under stress |
| topic | PRAG1 condensation phase separation cell contraction stress |
| url | https://www.mdpi.com/2218-273X/15/3/379 |
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