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SMN interacts with and regulates the actin\u2010binding protein profilin2a, thereby influencing actin dynamics. Dysfunctional actin dynamics caused by SMN loss disrupts neurite outgrowth, axonal pathfinding, and formation of functional synapses in neurons. Whether the SMN protein directly interacts with and regulates filamentous (F\u2010) and monomeric globular (G\u2010) actin is still elusive. In a quantitative single cell approach, we show that SMN loss leads to dysregulated F\u2010\/G\u2010actin fractions. Furthermore, quantitative assessment of cell morphology suggests an F\u2010actin organizational defect. Interestingly, this is mediated by an interaction of SMN with G\u2010 and F\u2010actin. In co\u2010immunoprecipitation, in\u2010vitro pulldown and co\u2010localization assays, we elucidated that this interaction is independent of the SMN\u2010profilin2a interaction. Therefore, we suggest two populations being relevant for functional actin dynamics in healthy neurons: SMN\u2010profilin2a\u2010actin and SMN\u2010actin. Additionally, those two populations may influence each other and therefore regulate binding of SMN to actin. In SMA, we showed a dysregulated co\u2010localization pattern of SMN\u2010actin which could only partially rescued by SMN restoration. However, dysregulation of F\u2010\/G\u2010actin fractions was reduced by SMN restoration. Taken together, our results suggest a novel molecular function of SMN in binding to actin independent from SMN\u2010profilin2a interaction.<\/jats:p>","DOI":"10.1096\/fj.202300183r","type":"journal-article","created":{"date-parts":[[2024,9,21]],"date-time":"2024-09-21T04:50:36Z","timestamp":1726894236000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The spinal muscular atrophy gene product regulates actin dynamics"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7947-509X","authenticated-orcid":false,"given":"Tobias","family":"Sch\u00fcning","sequence":"first","affiliation":[{"name":"SMATHERIA gGmbH \u2013 Non\u2010Profit Biomedical Research Institute  Hannover Germany"},{"name":"Department of Anatomy and Cell Biology, Faculty of Medicine Martin Luther University Halle\u2010Wittenberg  Halle (Saale) 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