{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:26:11Z","timestamp":1791851171260,"version":"4.3.4"},"reference-count":56,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000},"content-version":"vor","delay-in-days":544,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS105981"],"award-info":[{"award-number":["R01NS105981"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R00NS080985"],"award-info":[{"award-number":["R00NS080985"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2019,3]]},"DOI":"10.1074\/jbc.ra118.006351","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T00:45:12Z","timestamp":1547167512000},"page":"3696-3706","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":105,"title":["Aggregation of the nucleic acid\u2013binding protein TDP-43 occurs via distinct routes that are coordinated with stress granule formation"],"prefix":"10.1016","volume":"294","author":[{"given":"Youjun","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4099-0278","authenticated-orcid":false,"given":"Todd J.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1074\/jbc.RA118.006351_bib1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"10.1074\/jbc.RA118.006351_bib2","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.cell.2009.03.006","article-title":"Rethinking ALS: the FUS about TDP-43","volume":"136","author":"Lagier-Tourenne","year":"2009","journal-title":"Cell"},{"key":"10.1074\/jbc.RA118.006351_bib3","doi-asserted-by":"crossref","first-page":"R156","DOI":"10.1093\/hmg\/ddp303","article-title":"Mutations in TDP-43 link glycine-rich domain functions to amyotrophic lateral sclerosis","volume":"18","author":"Pesiridis","year":"2009","journal-title":"Hum. Mol. Genet"},{"key":"10.1074\/jbc.RA118.006351_bib4","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms6845","article-title":"An acetylation switch controls TDP-43 function and aggregation propensity","volume":"6","author":"Cohen","year":"2015","journal-title":"Nat. Commun"},{"key":"10.1074\/jbc.RA118.006351_bib5","doi-asserted-by":"crossref","first-page":"182","DOI":"10.2353\/ajpath.2008.080003","article-title":"Enrichment of C-terminal fragments in TAR DNA-binding protein-43 cytoplasmic inclusions in brain but not in spinal cord of frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"173","author":"Igaz","year":"2008","journal-title":"Am. J. Pathol"},{"key":"10.1074\/jbc.RA118.006351_bib6","doi-asserted-by":"crossref","DOI":"10.1038\/srep23281","article-title":"Mass spectrometric analysis of accumulated TDP-43 in amyotrophic lateral sclerosis brains","volume":"6","author":"Kametani","year":"2016","journal-title":"Sci. Rep"},{"key":"10.1074\/jbc.RA118.006351_bib7","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3389\/fnmol.2017.00005","article-title":"Cysteine modifications in the pathogenesis of ALS","volume":"10","author":"Valle","year":"2017","journal-title":"Front. Mol. Neurosci"},{"key":"10.1074\/jbc.RA118.006351_bib8","article-title":"Hyperphosphorylation as a defense mechanism to reduce TDP-43 aggregation","volume":"6","author":"Li","year":"2011","journal-title":"PLoS One"},{"key":"10.1074\/jbc.RA118.006351_bib9","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41467-017-00088-4","article-title":"Acetylation-induced TDP-43 pathology is suppressed by an HSF1-dependent chaperone program","volume":"8","author":"Wang","year":"2017","journal-title":"Nat. Commun"},{"key":"10.1074\/jbc.RA118.006351_bib10","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00401-008-0477-9","article-title":"Phosphorylation of S409\/410 of TDP-43 is a consistent feature in all sporadic and familial forms of TDP-43 proteinopathies","volume":"117","author":"Neumann","year":"2009","journal-title":"Acta Neuropathol"},{"key":"10.1074\/jbc.RA118.006351_bib11","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1080\/07391102.2017.1310670","article-title":"The proteinopathy of D169G and K263E mutants at the RNA recognition motif (RRM) domain of tar DNA-binding protein (tdp43) causing neurological disorders: a computational study","volume":"36","author":"Bhandare","year":"2017","journal-title":"J. Biomol. Struct. Dyn"},{"key":"10.1074\/jbc.RA118.006351_bib12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40478-015-0190-6","article-title":"A novel mutation P112H in the TARDBP gene associated with frontotemporal lobar degeneration without motor neuron disease and abundant neuritic amyloid plaques","volume":"3","author":"Moreno","year":"2015","journal-title":"Acta Neuropathol. Commun"},{"key":"10.1074\/jbc.RA118.006351_bib13","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.tibs.2007.12.003","article-title":"Stress granules: the Tao of RNA triage","volume":"33","author":"Anderson","year":"2008","journal-title":"Trends Biochem. Sci"},{"key":"10.1074\/jbc.RA118.006351_bib14","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/nrm2694","article-title":"RNA granules: post-transcriptional and epigenetic modulators of gene expression","volume":"10","author":"Anderson","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"10.1074\/jbc.RA118.006351_bib15","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1111\/j.1471-4159.2009.06383.x","article-title":"TDP-43 is recruited to stress granules in conditions of oxidative insult","volume":"111","author":"Colombrita","year":"2009","journal-title":"J. Neurochem"},{"key":"10.1074\/jbc.RA118.006351_bib16","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1128\/MCB.01279-10","article-title":"TDP-43 is directed to stress granules by sorbitol, a novel physiological osmotic and oxidative stressor","volume":"31","author":"Dewey","year":"2011","journal-title":"Mol. Cell. Biol"},{"key":"10.1074\/jbc.RA118.006351_bib17","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1021\/pr901076y","article-title":"Global analysis of TDP-43 interacting proteins reveals strong association with RNA splicing and translation machinery","volume":"9","author":"Freibaum","year":"2010","journal-title":"J. Proteome Res"},{"key":"10.1074\/jbc.RA118.006351_bib18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0013250","article-title":"Tar DNA binding protein-43 (TDP-43) associates with stress granules: analysis of cultured cells and pathological brain tissue","volume":"5","author":"Liu-Yesucevitz","year":"2010","journal-title":"PLoS One"},{"key":"10.1074\/jbc.RA118.006351_bib19","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1093\/hmg\/ddr021","article-title":"TAR DNA-binding protein 43 (TDP-43) regulates stress granule dynamics via differential regulation of G3BP and TIA-1","volume":"20","author":"McDonald","year":"2011","journal-title":"Hum. Mol. Genet"},{"key":"10.1074\/jbc.RA118.006351_bib20","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1074\/jbc.M109.022012","article-title":"Characterization of alternative isoforms and inclusion body of the TAR DNA-binding protein-43","volume":"285","author":"Nishimoto","year":"2010","journal-title":"J. Biol. Chem"},{"key":"10.1074\/jbc.RA118.006351_bib21","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1038\/emboj.2011.471","article-title":"Redox signalling directly regulates TDP-43 via cysteine oxidation and disulphide cross-linking","volume":"31","author":"Cohen","year":"2012","journal-title":"EMBO J"},{"key":"10.1074\/jbc.RA118.006351_bib22","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3389\/fncel.2015.00423","article-title":"Alterations in stress granule dynamics driven by TDP-43 and FUS: a link to pathological inclusions in ALS?","volume":"9","author":"Aulas","year":"2015","journal-title":"Front. Cell Neurosci"},{"key":"10.1074\/jbc.RA118.006351_bib23","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1083\/jcb.201302044","article-title":"Stress granules as crucibles of ALS pathogenesis","volume":"201","author":"Li","year":"2013","journal-title":"J. Cell Biol"},{"key":"10.1074\/jbc.RA118.006351_bib24","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.brainres.2016.05.022","article-title":"Stress granules at the intersection of autophagy and ALS","volume":"1649","author":"Monahan","year":"2016","journal-title":"Brain Res"},{"key":"10.1074\/jbc.RA118.006351_bib25","first-page":"6886","article-title":"Fragile X protein mitigates TDP-43 toxicity by remodeling RNA granules and restoring translation","volume":"24","author":"Coyne","year":"2015","journal-title":"Hum. Mol. Genet"},{"key":"10.1074\/jbc.RA118.006351_bib26","doi-asserted-by":"crossref","first-page":"16086","DOI":"10.1523\/JNEUROSCI.4105-11.2011","article-title":"Local RNA translation at the synapse and in disease","volume":"31","author":"Liu-Yesucevitz","year":"2011","journal-title":"J. Neurosci"},{"key":"10.1074\/jbc.RA118.006351_bib27","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s00401-016-1603-8","article-title":"Co-regulation of mRNA translation by TDP-43 and Fragile X Syndrome protein FMRP","volume":"132","author":"Majumder","year":"2016","journal-title":"Acta Neuropathol"},{"key":"10.1074\/jbc.RA118.006351_bib28","doi-asserted-by":"crossref","first-page":"22560","DOI":"10.1074\/jbc.M112.357582","article-title":"Neurodegeneration-associated TDP-43 interacts with fragile X mental retardation protein (FMRP)\/Staufen (STAU1) and regulates SIRT1 expression in neuronal cells","volume":"287","author":"Yu","year":"2012","journal-title":"J. Biol. Chem"},{"key":"10.1074\/jbc.RA118.006351_bib29","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0013250","article-title":"Tar DNA binding protein-43 (TDP-43) associates with stress granules: analysis of cultured cells and pathological brain tissue","volume":"5","author":"Liu-Yesucevitz","year":"2010","journal-title":"PLoS One"},{"key":"10.1074\/jbc.RA118.006351_bib30","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1111\/j.1601-183X.2005.00144.x","article-title":"FMRP RNA targets: identification and validation","volume":"4","author":"Darnell","year":"2005","journal-title":"Genes Brain Behav"},{"key":"10.1074\/jbc.RA118.006351_bib31","doi-asserted-by":"crossref","first-page":"3087","DOI":"10.1093\/hmg\/ddg335","article-title":"Fragile X mental retardation protein determinants required for its association with polyribosomal mRNPs","volume":"12","author":"Mazroui","year":"2003","journal-title":"Hum. Mol. Genet"},{"key":"10.1074\/jbc.RA118.006351_bib32","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1093\/hmg\/11.24.3007","article-title":"Trapping of messenger RNA by fragile X mental retardation protein into cytoplasmic granules induces translation repression","volume":"11","author":"Mazroui","year":"2002","journal-title":"Hum. Mol. Genet"},{"key":"10.1074\/jbc.RA118.006351_bib33","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1093\/hmg\/ddg350","article-title":"Phosphorylation influences the translation state of FMRP-associated polyribosomes","volume":"12","author":"Ceman","year":"2003","journal-title":"Hum. Mol. Genet"},{"key":"10.1074\/jbc.RA118.006351_bib34","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1101\/gad.461107","article-title":"The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response","volume":"21","author":"Kwon","year":"2007","journal-title":"Genes Dev"},{"key":"10.1074\/jbc.RA118.006351_bib35","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0092-8674(03)00939-5","article-title":"The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress","volume":"115","author":"Kawaguchi","year":"2003","journal-title":"Cell"},{"key":"10.1074\/jbc.RA118.006351_bib36","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/emboj.2009.405","article-title":"HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy","volume":"29","author":"Lee","year":"2010","journal-title":"EMBO J"},{"key":"10.1074\/jbc.RA118.006351_bib37","doi-asserted-by":"crossref","first-page":"40282","DOI":"10.1074\/jbc.M508786200","article-title":"HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin","volume":"280","author":"Iwata","year":"2005","journal-title":"J. Biol. Chem"},{"key":"10.1074\/jbc.RA118.006351_bib38","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/nature05853","article-title":"HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS","volume":"447","author":"Pandey","year":"2007","journal-title":"Nature"},{"key":"10.1074\/jbc.RA118.006351_bib39","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1111\/j.1471-4159.2008.05564.x","article-title":"Histone deacetylase 6 interacts with the microtubule-associated protein tau","volume":"106","author":"Ding","year":"2008","journal-title":"J. Neurochem"},{"key":"10.1074\/jbc.RA118.006351_bib40","doi-asserted-by":"crossref","first-page":"15035","DOI":"10.1074\/jbc.M112.431957","article-title":"HDAC6 regulates mutant SOD1 aggregation through two SMIR motifs and tubulin acetylation","volume":"288","author":"Gal","year":"2013","journal-title":"J. Biol. Chem"},{"key":"10.1074\/jbc.RA118.006351_bib41","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.molmed.2011.06.004","article-title":"TDP-43 functions and pathogenic mechanisms implicated in TDP-43 proteinopathies","volume":"17","author":"Cohen","year":"2011","journal-title":"Trends Mol. Med"},{"key":"10.1074\/jbc.RA118.006351_bib42","doi-asserted-by":"crossref","first-page":"5211","DOI":"10.1093\/hmg\/ddu243","article-title":"Multistep process of FUS aggregation in the cell cytoplasm involves RNA-dependent and RNA-independent mechanisms","volume":"23","author":"Shelkovnikova","year":"2014","journal-title":"Hum. Mol. Genet"},{"key":"10.1074\/jbc.RA118.006351_bib43","doi-asserted-by":"crossref","first-page":"E2466","DOI":"10.1073\/pnas.1614462114","article-title":"Amyotrophic lateral sclerosis-linked mutations increase the viscosity of liquid-like TDP-43 RNP granules in neurons","volume":"114","author":"Gopal","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"10.1074\/jbc.RA118.006351_bib44","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.cell.2015.09.015","article-title":"Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization","volume":"163","author":"Molliex","year":"2015","journal-title":"Cell"},{"key":"10.1074\/jbc.RA118.006351_bib45","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.neuron.2015.10.030","article-title":"ALS\/FTD mutation-induced phase transition of FUS liquid droplets and reversible hydrogels into irreversible hydrogels impairs RNP granule function","volume":"88","author":"Murakami","year":"2015","journal-title":"Neuron"},{"key":"10.1074\/jbc.RA118.006351_bib46","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.cell.2015.07.047","article-title":"A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation","volume":"162","author":"Patel","year":"2015","journal-title":"Cell"},{"key":"10.1074\/jbc.RA118.006351_bib47","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.molcel.2018.07.002","article-title":"Poly(ADP-ribose) prevents pathological phase separation of TDP-43 by promoting liquid demixing and stress granule localization","volume":"71","author":"McGurk","year":"2018","journal-title":"Mol. Cell"},{"key":"10.1074\/jbc.RA118.006351_bib48","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s40478-017-0493-x","article-title":"Clinical and neuropathological features of ALS\/FTD with TIA1 mutations","volume":"5","author":"Hirsch-Reinshagen","year":"2017","journal-title":"Acta Neuropathol. Commun"},{"key":"10.1074\/jbc.RA118.006351_bib49","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.neuron.2017.07.025","article-title":"TIA1 mutations in amyotrophic lateral sclerosis and frontotemporal dementia promote phase separation and alter stress granule dynamics","volume":"95","author":"Mackenzie","year":"2017","journal-title":"Neuron"},{"key":"10.1074\/jbc.RA118.006351_bib50","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/s41467-017-00911-y","article-title":"HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients","volume":"8","author":"Guo","year":"2017","journal-title":"Nat. Commun"},{"key":"10.1074\/jbc.RA118.006351_bib51","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1093\/hmg\/ddt028","article-title":"Hdac6 deletion delays disease progression in the SOD1G93A mouse model of ALS","volume":"22","author":"Taes","year":"2013","journal-title":"Hum. Mol. Genet"},{"key":"10.1074\/jbc.RA118.006351_bib52","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1083\/jcb.201001039","article-title":"Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy","volume":"189","author":"Lee","year":"2010","journal-title":"J. Cell Biol"},{"key":"10.1074\/jbc.RA118.006351_bib53","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.molcel.2007.05.033","article-title":"HDAC6 modulates cell motility by altering the acetylation level of cortactin","volume":"27","author":"Zhang","year":"2007","journal-title":"Mol. Cell"},{"key":"10.1074\/jbc.RA118.006351_bib54","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0168913","article-title":"Conserved lysine acetylation within the microtubule-binding domain regulates MAP2\/Tau family members","volume":"11","author":"Hwang","year":"2016","journal-title":"PLoS One"},{"key":"10.1074\/jbc.RA118.006351_bib55","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.molcel.2005.04.021","article-title":"HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor","volume":"18","author":"Kovacs","year":"2005","journal-title":"Mol. Cell"},{"key":"10.1074\/jbc.RA118.006351_bib56","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s13238-014-0102-8","article-title":"Proteomic identification and functional characterization of MYH9, Hsc70, and DNAJA1 as novel substrates of HDAC6 deacetylase activity","volume":"6","author":"Zhang","year":"2015","journal-title":"Protein Cell"}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925820389936?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925820389936?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1074\/jbc.RA118.006351","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T09:42:55Z","timestamp":1641289375000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925820389936"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":56,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["S0021925820389936"],"URL":"https:\/\/doi.org\/10.1074\/jbc.ra118.006351","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2019,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Aggregation of the nucleic acid\u2013binding protein TDP-43 occurs via distinct routes that are coordinated with stress granule formation","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1074\/jbc.RA118.006351","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Chen and Cohen.","name":"copyright","label":"Copyright"}]}}