{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T18:29:30Z","timestamp":1772821770501,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ataxia Charlevoix-Saguenay Foundation","award":["PT88204"],"award-info":[{"award-number":["PT88204"]}]},{"name":"Ataxia Charlevoix-Saguenay Foundation","award":["PT86058"],"award-info":[{"award-number":["PT86058"]}]},{"DOI":"10.13039\/501100000223","name":"Muscular Dystrophy Canada","doi-asserted-by":"publisher","award":["PT88204"],"award-info":[{"award-number":["PT88204"]}],"id":[{"id":"10.13039\/501100000223","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000223","name":"Muscular Dystrophy Canada","doi-asserted-by":"publisher","award":["PT86058"],"award-info":[{"award-number":["PT86058"]}],"id":[{"id":"10.13039\/501100000223","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autosomal Recessive Spastic Ataxia of the Charlevoix Saguenay (ARSACS) is caused by mutation in the SACS gene resulting in loss of function of the protein sacsin. A key feature is the formation of abnormal bundles of neurofilaments (NF) in neurons and vimentin intermediate filaments (IF) in cultured fibroblasts, suggesting a role of sacsin in IF homeostasis. Sacsin contains a J domain (SacsJ) homologous to Hsp40, that can interact with Hsp70 chaperones. The SacsJ domain resolved NF bundles in cultured Sacs\u2212\/\u2212 neurons. Having studied the mechanism using NF assembled in vitro from purified NF proteins, we report that the SacsJ domain interacts with NF proteins to disassemble NFL filaments, and to inhibit their initial assembly. A cell-penetrating peptide derived from this domain, SacsJ-myc-TAT was efficient in disassembling NF bundles in cultured Sacs\u2212\/\u2212 motor neurons, restoring the NF network; however, there was some loss of vimentin IF and NF in cultured Sacs+\/+ fibroblasts and motor neurons, respectively. These results suggest that sacsin through its SacsJ domain is a key regulator of NF and vimentin IF networks in cells.<\/jats:p>","DOI":"10.3390\/ijms232415742","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T04:05:22Z","timestamp":1670817922000},"page":"15742","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The J Domain of Sacsin Disrupts Intermediate Filament Assembly"],"prefix":"10.3390","volume":"23","author":[{"given":"Afrooz","family":"Dabbaghizadeh","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada"},{"name":"Department of Kinesiology and Physical Education, McGill University, Room 210, 475 Pine Avenue West, Montreal, QC H2W 1S4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Par\u00e9","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada"},{"name":"Department of Kinesiology and Physical Education, McGill University, Room 210, 475 Pine Avenue West, Montreal, QC H2W 1S4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zacharie","family":"Cheng-Boivin","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada"},{"name":"Department of Kinesiology and Physical Education, McGill University, Room 210, 475 Pine Avenue West, Montreal, QC H2W 1S4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Dagher","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Minotti","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Jos\u00e9e","family":"Dicaire","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics of Motion, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Brais","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics of Motion, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason C.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8692-6055","authenticated-orcid":false,"given":"Heather D.","family":"Durham","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2022-1890","authenticated-orcid":false,"given":"Benoit J.","family":"Gentil","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada"},{"name":"Department of Kinesiology and Physical Education, McGill University, Room 210, 475 Pine Avenue West, Montreal, QC H2W 1S4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1111\/j.1468-1331.2010.03335.x","article-title":"Myelinated retinal fibers in autosomal recessive spastic ataxia of Charlevoix-Saguenay","volume":"18","author":"Vingolo","year":"2011","journal-title":"Eur. 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