{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:03:20Z","timestamp":1793736200088,"version":"4.6.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T00:00:00Z","timestamp":1589760000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T00:00:00Z","timestamp":1589760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Huntington\u2019s disease (HD) is caused by CAG repeat expansion in the huntingtin gene. The expanded polyglutamine (polyQ) repeat of the encoded protein leads to protein misfolding and aggregation, resulting in increased neuronal cell death. DNAJ co-chaperones play a crucial role in transferring misfolded\/unfolded proteins to HSP70 chaperones, which play an essential role for protein folding. Here, we investigated the effect of knock out (KO) of three individual DNAJ genes in HEK293 cells expressing polyglutamine74exon1 huntingtin (polyQ74htt). Flourescence\u00a0microscopy analysis revealed that KO of DNAJB6 resulted in a 5-fold increase in polyQ74htt aggregation and that DNAJA1 KO resulted in a 4-fold decrease of polyQ74htt aggregation. KO of DNAJB1 did not change the propensity of polyQ74htt to aggregate in cells. These findings where confirmed both by fluorescence microscopy analysis and filter trap assay (FTA). DNAJB6 KO cells displayed an increased rate of cell death as assessed by trypan blue exclusion and propidium iodide (PI) uptake assays. These results demonstrate that the DNAJ proteins DNAJA1 and DNAJB6 can modulate polyQ aggregation in opposite manners, and thus that fine-tuning the cellular levels of DNAJ proteins is critical for suppression of polyQ aggregation and cell survival.<\/jats:p>","DOI":"10.1038\/s41598-020-65046-5","type":"journal-article","created":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T10:02:50Z","timestamp":1589796170000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Co-chaperones DNAJA1 and DNAJB6 are critical for regulation of polyglutamine aggregation"],"prefix":"10.1038","volume":"10","author":[{"given":"Claudio","family":"Rodr\u00edguez-Gonz\u00e1lez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiying","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sertan","family":"Arkan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,18]]},"reference":[{"key":"65046_CR1","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/B978-0-444-63233-3.00011-7","volume":"147","author":"CA Stoyas","year":"2018","unstructured":"Stoyas, C. A. & La Spada, A. R. The CAG-polyglutamine repeat diseases: a clinical, molecular, genetic, and pathophysiologic nosology. Handb. Clin. Neurol. 147, 143\u2013170, https:\/\/doi.org\/10.1016\/B978-0-444-63233-3.00011-7 (2018).","journal-title":"Handb. Clin. Neurol."},{"key":"65046_CR2","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1134\/S0006297918090043","volume":"83","author":"SN Illarioshkin","year":"2018","unstructured":"Illarioshkin, S. N., Klyushnikov, S. A., Vigont, V. A., Seliverstov, Y. A. & Kaznacheyeva, E. V. Molecular Pathogenesis in Huntington\u2019s Disease. Biochemistry 83, 1030\u20131039, https:\/\/doi.org\/10.1134\/S0006297918090043 (2018).","journal-title":"Biochemistry"},{"key":"65046_CR3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.2147\/DNND.S163808","volume":"9","author":"WF Kaemmerer","year":"2019","unstructured":"Kaemmerer, W. F. & Grondin, R. C. The effects of huntingtin-lowering: what do we know so far? Degener. Neurol. Neuromuscul. Dis. 9, 3\u201317, https:\/\/doi.org\/10.2147\/DNND.S163808 (2019).","journal-title":"Degener. Neurol. Neuromuscul. Dis."},{"key":"65046_CR4","doi-asserted-by":"publisher","first-page":"101","DOI":"10.2217\/fnl-2017-0035","volume":"13","author":"KT Potkin","year":"2018","unstructured":"Potkin, K. T. & Potkin, S. G. New directions in therapeutics for Huntington disease. Future Neurol. 13, 101\u2013121, https:\/\/doi.org\/10.2217\/fnl-2017-0035 (2018).","journal-title":"Future Neurol."},{"key":"65046_CR5","doi-asserted-by":"publisher","unstructured":"Fernandez-Fernandez, M. R. & Valpuesta, J. M. Hsp70 chaperone: a master player in protein homeostasis. F1000Res 7, https:\/\/doi.org\/10.12688\/f1000research.15528.1 (2018).","DOI":"10.12688\/f1000research.15528.1"},{"key":"65046_CR6","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1074\/jbc.REV118.002810","volume":"294","author":"MP Mayer","year":"2019","unstructured":"Mayer, M. P. & Gierasch, L. M. Recent advances in the structural and mechanistic aspects of Hsp70 molecular chaperones. J. Biol. Chem. 294, 2085\u20132097, https:\/\/doi.org\/10.1074\/jbc.REV118.002810 (2019).","journal-title":"J. Biol. Chem."},{"key":"65046_CR7","doi-asserted-by":"publisher","unstructured":"Zarouchlioti, C., Parfitt, D. A., Li, W., Gittings, L. M. & Cheetham, M. E. DNAJ Proteins in neurodegeneration: essential and protective factors. Philos Trans R Soc Lond B Biol Sci 373, https:\/\/doi.org\/10.1098\/rstb.2016.0534 (2018).","DOI":"10.1098\/rstb.2016.0534"},{"key":"65046_CR8","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.1007\/s00018-006-6192-6","volume":"63","author":"XB Qiu","year":"2006","unstructured":"Qiu, X. B., Shao, Y. M., Miao, S. & Wang, L. The diversity of the DnaJ\/Hsp40 family, the crucial partners for Hsp70 chaperones. Cell Mol. Life Sci. 63, 2560\u20132570, https:\/\/doi.org\/10.1007\/s00018-006-6192-6 (2006).","journal-title":"Cell Mol. 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Biochemistry 47, 7001\u20137011, https:\/\/doi.org\/10.1021\/bi800639z (2008).","journal-title":"Biochemistry"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-65046-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-65046-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-65046-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T11:19:13Z","timestamp":1670325553000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-65046-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,18]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["65046"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-65046-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,18]]},"assertion":[{"value":"13 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8130"}}