{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:54:04Z","timestamp":1791942844933,"version":"4.3.4"},"reference-count":38,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T00:00:00Z","timestamp":1553040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T00:00:00Z","timestamp":1553040000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T00:00:00Z","timestamp":1553040000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35NS097974"],"award-info":[{"award-number":["R35NS097974"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000971","name":"ALS Association","doi-asserted-by":"publisher","award":["18-IIA-419"],"award-info":[{"award-number":["18-IIA-419"]}],"id":[{"id":"10.13039\/100000971","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007737","name":"St. Jude Children's Research Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007737","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Stress granules (SGs) are non-membrane-bound RNA-protein granules that assemble through phase separation in response to cellular stress. Disturbances in SG dynamics have been implicated as a primary driver of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), suggesting the hypothesis that these diseases reflect an underlying disturbance in the dynamics and material properties of SGs. However, this concept has remained largely untestable in available models of SG assembly, which require the confounding variable of exogenous stressors. Here we introduce a light-inducible SG system, termed OptoGranules, based on optogenetic multimerization of G3BP1, which is an essential scaffold protein for SG assembly. In this system, which permits experimental control of SGs in living cells in the absence of exogenous stressors, we demonstrate that persistent or repetitive assembly of SGs is cytotoxic and is accompanied by the evolution of SGs to cytoplasmic inclusions that recapitulate the pathology of ALS-FTD.<\/jats:p>\n                  <jats:p>Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (&lt;xref ref-type=\"decision-letter\" rid=\"SA1\"&gt;see decision letter&lt;\/xref&gt;).<\/jats:p>","DOI":"10.7554\/elife.39578","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T12:00:19Z","timestamp":1553083219000},"source":"Crossref","is-referenced-by-count":267,"title":["Chronic optogenetic induction of stress granules is cytotoxic and reveals the evolution of ALS-FTD pathology"],"prefix":"10.7554","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1742-1680","authenticated-orcid":true,"given":"Peipei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology, St. Jude Children\u2019s Research Hospital, Memphis, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baochang","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, St. Jude Children\u2019s Research Hospital, Memphis, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiguo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, St. Jude Children\u2019s Research Hospital, Memphis, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamshid","family":"Temirov","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, St. Jude Children\u2019s Research Hospital, Memphis, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Messing","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Chevy Chase, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9157-1612","authenticated-orcid":true,"given":"Hong Joo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, St. Jude Children\u2019s Research Hospital, Memphis, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5794-0349","authenticated-orcid":true,"given":"J Paul","family":"Taylor","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Chevy Chase, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2019,3,20]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.cell.2016.06.010","article-title":"Compositional control of Phase-Separated cellular bodies","volume":"166","author":"Banani","year":"2016","journal-title":"Cell"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nrm.2017.7","article-title":"Biomolecular condensates: organizers of cellular biochemistry","volume":"18","author":"Banani","year":"2017","journal-title":"Nature Reviews Molecular 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