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However, the molecular mechanism for this function remains elusive. In this study, we demonstrate that PRAG1 forms dynamic condensates in cells mediated by its \u03b1N and \u03b1J 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\u2019s 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.<\/jats:p>","DOI":"10.3390\/biom15030379","type":"journal-article","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T07:56:52Z","timestamp":1741161412000},"page":"379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PRAG1 Condensation Drives Cell Contraction Under Stress"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9177-4022","authenticated-orcid":false,"given":"Peiwu","family":"Ye","sequence":"first","affiliation":[{"name":"Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiran","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China"},{"name":"Department of Neurobiology of the Second Affiliated Hospital,  Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luyu","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuyuan","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8230-4061","authenticated-orcid":false,"given":"Peilin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhong","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou 310058, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3254-825X","authenticated-orcid":false,"given":"Huanxing","family":"Su","sequence":"additional","affiliation":[{"name":"Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3065-1843","authenticated-orcid":false,"given":"Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China"},{"name":"Department of Biophysics, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, China"},{"name":"Guizhou University Medical College, Guiyang 550025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.4155\/fmc-2016-0207","article-title":"Pseudokinases: Update on their functions and evaluation as new drug targets","volume":"9","author":"Byrne","year":"2017","journal-title":"Future Med. 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