{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:13:24Z","timestamp":1788516804557,"version":"build-2803163510"},"reference-count":63,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100016925","name":"Takeda Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K02860"],"award-info":[{"award-number":["24K02860"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24wm0625509"],"award-info":[{"award-number":["JP24wm0625509"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25wm0625509"],"award-info":[{"award-number":["JP25wm0625509"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010236","name":"Tokyo Metropolitan University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010236","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"abstract":"<jats:p>\n                    Overactivation of Microtubule affinity regulating kinase 4 (MARK4) is believed to contribute to Alzheimer's disease pathogenesis. MARK4 promotes the accumulation of the microtubule\u2010binding protein tau, thereby enhancing tau\u2010induced neurodegeneration. However, the underlying mechanisms by which MARK4 enhances tau accumulation are not fully understood. T\u2010cell intracellular antigen 1 (TIA1), a critical regulator of stress granule (SG) formation, has been suggested to initiate tau abnormality. Here, we report that MARK4 and TIA1 synergistically induce stress granule (SG) formation. MARK4 is localized in SGs with TIA1 in mammalian cultured cells and primary neurons. MARK4 suppresses TIA1 dimerization and enhances SG formation under oxidative stress. Co\u2010expression of MARK4 and TIA1 promotes tau accumulation, and knockdown of a fly ortholog of TIA1 suppressed tau toxicity in a\n                    <jats:italic>Drosophila<\/jats:italic>\n                    model. These results identify MARK4 as a novel regulator of SG formation and suggest a mechanistic link between oxidative stress and tau pathology.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.70338","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:29:53Z","timestamp":1788514193000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>MARK4<\/scp>\n                    enhances stress granule formation under oxidative stress and increases tau accumulation"],"prefix":"10.1002","author":[{"given":"Sho","family":"Nakajima","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, School of Science, Graduate School of Science Tokyo Metropolitan University  Tokyo 192\u20100397 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotone","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Science, Graduate School of Science Tokyo Metropolitan University  Tokyo 192\u20100397 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grigorii","family":"Sultanakhmetov","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Science, Graduate School of Science Tokyo Metropolitan University  Tokyo 192\u20100397 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoi","family":"Fukuchi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Science, Graduate School of Science Tokyo Metropolitan University  Tokyo 192\u20100397 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiya","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Science, Graduate School of Science Tokyo Metropolitan University  Tokyo 192\u20100397 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sawako","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Science, Graduate School of Science Tokyo Metropolitan University  Tokyo 192\u20100397 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Science, Graduate School of Science Tokyo Metropolitan University  Tokyo 192\u20100397 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Asada","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Science, Graduate School of Science Tokyo Metropolitan University  Tokyo 192\u20100397 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3956-276X","authenticated-orcid":false,"given":"Kanae","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Science, Graduate School of Science Tokyo Metropolitan University  Tokyo 192\u20100397 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1016\/j.neuron.2024.04.025","article-title":"Friend or foe: the role of stress granule in neurodegenerative disease","volume":"112","author":"Cui Q","year":"2024","journal-title":"Neuron"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.tcb.2016.05.004","article-title":"Principles and properties of stress granules","volume":"26","author":"Protter 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disease\u2010specific diversity in protein interactions within stress granules","volume":"172","author":"Markmiller S","year":"2018","journal-title":"Cell"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1038\/s41418-018-0217-1","article-title":"Dysregulation of autophagy and stress granule\u2010related proteins in stress\u2010driven tau pathology","volume":"26","author":"Silva JM","year":"2019","journal-title":"Cell Death Differ"},{"key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s40478-018-0574-5","article-title":"RNA binding proteins co\u2010localize with small tau inclusions in tauopathy","volume":"6","author":"Maziuk BF","year":"2018","journal-title":"Acta Neuropathol Commun"},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"5383","DOI":"10.1091\/mbc.e04-08-0715","article-title":"Stress granule assembly is mediated by prion\u2010like aggregation of TIA\u20101","volume":"15","author":"Gilks 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T","year":"2013","journal-title":"Cell Rep"},{"key":"e_1_2_10_36_1","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1126\/science.1062382","article-title":"Tauopathy in drosophila: neurodegeneration without neurofibrillary tangles","volume":"293","author":"Wittmann CW","year":"2001","journal-title":"Science"},{"key":"e_1_2_10_37_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/cr.2009.6","article-title":"DOG 1.0: illustrator of protein domain structures","volume":"19","author":"Ren J","year":"2009","journal-title":"Cell Res"},{"key":"e_1_2_10_38_1","doi-asserted-by":"crossref","first-page":"a012286","DOI":"10.1101\/cshperspect.a012286","article-title":"P\u2010bodies and stress granules: possible roles in the control of translation and mRNA degradation","volume":"4","author":"Decker CJ","year":"2012","journal-title":"Cold Spring Harb Perspect 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