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SMN deficiency causes a devastating motor neuron disease called spinal muscular atrophy (SMA). SMN forms the core of a protein complex localized at the cytoplasm and nuclear gems and that catalyzes spliceosomal snRNP particle synthesis. In cultured motor neurons, SMN is also present in dendrites and axons, and forms part of the ribonucleoprotein transport granules implicated in mRNA trafficking and local translation. Nevertheless, the distribution, regulation, and role of SMN at the axons and presynaptic motor terminals in vivo are still unclear. By using conventional confocal microscopy and STED super-resolution nanoscopy, we found that SMN appears in the form of granules distributed along motor axons at nerve terminals. Our fluorescence in situ hybridization and electron microscopy studies also confirmed the presence of \u03b2-actin mRNA, ribosomes, and polysomes in the presynaptic motor terminal, key elements of the protein synthesis machinery involved in local translation in this compartment. SMN granules co-localize with the microtubule-associated protein 1B (MAP1B) and neurofilaments, suggesting that the cytoskeleton participates in transporting and positioning the granules. We also found that, while SMN granules are physiologically downregulated at the presynaptic element during the period of postnatal maturation in wild-type (non-transgenic) mice, they accumulate in areas of neurofilament aggregation in SMA mice, suggesting that the high expression of SMN at the NMJ, together with the cytoskeletal defects, contribute to impairing the bi-directional traffic of proteins and organelles between the axon and the presynaptic terminal.<\/jats:p>","DOI":"10.3390\/biom12101524","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T20:35:55Z","timestamp":1666298155000},"page":"1524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["SMN Is Physiologically Downregulated at Wild-Type Motor Nerve Terminals but Aggregates Together with Neurofilaments in SMA Mouse Models"],"prefix":"10.3390","volume":"12","author":[{"given":"Julio","family":"Franco-Espin","sequence":"first","affiliation":[{"name":"Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5153-1181","authenticated-orcid":false,"given":"Ala\u00f3","family":"Gatius","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, School of Medicine, University of Lleida, Institut de Recerca Biom\u00e8dica de Lleida (IRBLleida), 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9452-7828","authenticated-orcid":false,"given":"Jos\u00e9 \u00c1ngel","family":"Armengol","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Cell Biology, University Pablo de Olavide, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2645-4126","authenticated-orcid":false,"given":"Saravanan","family":"Arumugam","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9550-8701","authenticated-orcid":false,"given":"Mehri","family":"Moradi","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neurobiology, University Hospital Wuerzburg, 97078 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sendtner","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neurobiology, University Hospital Wuerzburg, 97078 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1972-0115","authenticated-orcid":false,"given":"Jordi","family":"Calder\u00f3","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, School of Medicine, University of Lleida, Institut de Recerca Biom\u00e8dica de Lleida (IRBLleida), 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4027-4044","authenticated-orcid":false,"given":"Lucia","family":"Tabares","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.bbagrm.2016.12.008","article-title":"Diverse Role of Survival Motor Neuron Protein","volume":"1860","author":"Singh","year":"2017","journal-title":"Biochim. 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