{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:25:58Z","timestamp":1790673958869,"version":"4.1.0"},"reference-count":86,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T00:00:00Z","timestamp":1529625600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T00:00:00Z","timestamp":1529625600000},"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 is caused by the pathological expansion of a polyglutamine (polyQ) stretch in <jats:italic>Huntingtin<\/jats:italic> (<jats:italic>Htt<\/jats:italic>), but the molecular mechanisms by which polyQ expansion in Htt causes toxicity in selective neuronal populations remain poorly understood. Interestingly, heterologous expression of expanded polyQ Htt is toxic in <jats:italic>Saccharomyces cerevisiae<\/jats:italic> cells, but has no effect in <jats:italic>Schizosaccharomyces pombe<\/jats:italic>, a related yeast species possessing very few endogenous polyQ or Q\/N-rich proteins. Here, we used a comprehensive and unbiased mass spectrometric approach to identify proteins that bind <jats:italic>Htt<\/jats:italic> in a length-dependent manner in both species. Analysis of the expanded polyQ-associated proteins reveals marked enrichment of proteins that are localized to and play functional roles in nucleoli and mitochondria in <jats:italic>S. cerevisiae<\/jats:italic>, but not in <jats:italic>S. pombe<\/jats:italic>. Moreover, expanded polyQ Htt appears to interact preferentially with endogenous polyQ and Q\/N-rich proteins, which are rare in <jats:italic>S. pombe<\/jats:italic>, as well as proteins containing coiled-coil motifs in <jats:italic>S. cerevisiae<\/jats:italic>. Taken together, these results suggest that polyQ expansion of Htt may cause cellular toxicity in <jats:italic>S. cerevisiae<\/jats:italic> by sequestering endogenous polyQ and Q\/N-rich proteins, particularly within nucleoli and mitochondria.<\/jats:p>","DOI":"10.1038\/s41598-018-27900-5","type":"journal-article","created":{"date-parts":[[2018,6,18]],"date-time":"2018-06-18T11:26:44Z","timestamp":1529321204000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Comparative Analysis of Mutant Huntingtin Binding Partners in Yeast Species"],"prefix":"10.1038","volume":"8","author":[{"given":"Yanding","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley A.","family":"Zurawel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole P.","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin L.","family":"Duennwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arminja N.","family":"Kettenbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surachai","family":"Supattapone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,6,22]]},"reference":[{"key":"27900_CR1","doi-asserted-by":"publisher","first-page":"4273","DOI":"10.1093\/nar\/gks011","volume":"40","author":"MH Schaefer","year":"2012","unstructured":"Schaefer, M. H., Wanker, E. E. & Andrade-Navarro, M. A. Evolution and function of CAG\/polyglutamine repeats in protein-protein interaction networks. Nucleic acids research 40, 4273\u20134287, https:\/\/doi.org\/10.1093\/nar\/gks011 (2012).","journal-title":"Nucleic acids research"},{"key":"27900_CR2","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1056\/NEJMcibr067022","volume":"356","author":"JT Greenamyre","year":"2007","unstructured":"Greenamyre, J. T. Huntington\u2019s disease\u2013making connections. The New England journal of medicine 356, 518\u2013520, https:\/\/doi.org\/10.1056\/NEJMcibr067022 (2007).","journal-title":"The New England journal of medicine"},{"key":"27900_CR3","doi-asserted-by":"publisher","first-page":"5355","DOI":"10.1073\/pnas.91.12.5355","volume":"91","author":"MF Perutz","year":"1994","unstructured":"Perutz, M. F., Johnson, T., Suzuki, M. & Finch, J. T. Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases. 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