{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:06:02Z","timestamp":1789653962672,"version":"4.0.0"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>SQSTM1<\/jats:italic>\n                    is one of the causative genes of neurodegenerative disorders, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The SQSTM1 protein regulates the degradation of polyubiquitinated proteins and autophagosome formation through its interaction with microtubule\u2010associated protein light chain 3 (MAP1LC3\/LC3). However, the molecular mechanisms by which SQSTM1\u2010LC3 binding regulates the autophagy\u2010endolysosomal system (APELS) remain unclear. To elucidate the spatiotemporal role of SQSTM1, we transiently expressed wild\u2010type SQSTM1 or missense mutants carrying mutations in the LC3\u2010interacting region (LIR), fused with the photoconvertible fluorescent protein Dendra2. Live\u2010cell fluorescence imaging and co\u2010localization analyses with markers of the APELS were then performed. Particle analysis of photoconverted or non\u2010photoconverted SQSTM1\u2010positive structures in live cells revealed that the pathogenic L341V variant formed larger structures than the wild\u2010type. Co\u2010localization analyses further showed that both the L341V and artificial LIR3A mutants accumulated in large ubiquitin\u2010positive structures, likely due to impaired localization to autophagosomes. These results suggest that mutations within the LIR differentially affect autophagosome formation and cargo degradation within APELS\u2010related compartments, highlighting the importance of SQSTM1 structural integrity in ALS\/FTD pathogenesis.\n                  <\/jats:p>","DOI":"10.1111\/gtc.70134","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T02:35:06Z","timestamp":1782959706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <scp>SQSTM1 L341V<\/scp>\n                    Variant Associated With Sporadic\n                    <scp>ALS<\/scp>\n                    Promotes the Accumulation of Enlarged Ubiquitin\u2010Positive\n                    <scp>SQSTM1<\/scp>\n                    Bodies"],"prefix":"10.1111","volume":"31","author":[{"given":"Kento","family":"Shimakura","sequence":"first","affiliation":[{"name":"Molecular Neuropathobiology Laboratory, Department of Physiology Tokai University School of Medicine  Isehara Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Oka","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Sciences Tokai University School of Medicine  Isehara Kanagawa Japan"},{"name":"The Institute of Medical Sciences Tokai University  Isehara Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Yudahira","sequence":"additional","affiliation":[{"name":"Molecular Neuropathobiology Laboratory, Department of Physiology Tokai University School of Medicine  Isehara Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaro","family":"Hama","sequence":"additional","affiliation":[{"name":"Molecular Neuropathobiology Laboratory, Department of Physiology Tokai University School of Medicine  Isehara Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asako","family":"Otomo","sequence":"additional","affiliation":[{"name":"Molecular Neuropathobiology Laboratory, Department of Physiology Tokai University School of Medicine  Isehara Kanagawa Japan"},{"name":"Micro\/Nano Technology Center Tokai University  Hiratsuka Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4997-3968","authenticated-orcid":false,"given":"Shinji","family":"Hadano","sequence":"additional","affiliation":[{"name":"Molecular Neuropathobiology Laboratory, Department of Physiology Tokai University School of Medicine  Isehara Kanagawa Japan"},{"name":"The Institute of Medical Sciences Tokai University  Isehara Kanagawa Japan"},{"name":"Micro\/Nano Technology Center Tokai University  Hiratsuka Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20896"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102992\u20103"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010011\u20100911\u20102"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.126128"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101514"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.09.008"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.2144\/000112470"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.03.062"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531\u2010022\u201000434\u20104"},{"key":"e_1_2_11_11_1","first-page":"105653","volume-title":"Neurobiology of Disease","author":"Davidson J. 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