{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:17:40Z","timestamp":1791253060667,"version":"4.1.0"},"reference-count":37,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":2694,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Huntingtin is a large membrane associated scaffolding protein that associates with endocytic and exocytic vesicles and modulates their trafficking along cytoskeletal tracks. Although Huntington\u2019s disease progression is linked to toxic accumulation of mutant huntingtin protein, loss of wildtype huntingtin function may also contribute to neuronal cell death but its precise function is not well understood. Therefore, we investigated the molecular role of huntingtin in exocytosis and observed that huntingtin knockdown in HeLa cells causes a delay in ER-to-Golgi transport and a reduction in the number of cargo vesicles leaving the trans-Golgi network. In addition, huntingtin is required for secretory vesicle fusion at the plasma membrane. Similar defects in the early exocytic pathway were observed in primary fibroblasts from homozygous Q140 huntingtin knock-in mice that lack wildtype huntingtin expression. Interestingly, heterozygous fibroblasts from a Huntington\u2019s disease patient with a Q180 expansion displayed no obvious defects in the early secretory pathway. Thus, our results highlight the requirement for wildtype huntingtin at distinct steps along the secretory pathway.<\/jats:p>","DOI":"10.1242\/dmm.017368","type":"journal-article","created":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T08:55:41Z","timestamp":1414832141000},"source":"Crossref","is-referenced-by-count":32,"title":["Huntingtin is required for ER-to-Golgi transport and for secretory vesicle fusion at the plasma membrane"],"prefix":"10.1242","author":[{"given":"Hemma","family":"Brandstaetter","sequence":"first","affiliation":[{"name":"University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonina J.","family":"Kruppa","sequence":"additional","affiliation":[{"name":"University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folma","family":"Buss","sequence":"additional","affiliation":[{"name":"University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2014,1,1]]},"reference":[{"key":"2021042501170826500_b1-0071335","doi-asserted-by":"crossref","first-page":"e68775","DOI":"10.1371\/journal.pone.0068775","article-title":"A huntingtin peptide inhibits polyQ-huntingtin associated defects","volume":"8","author":"Arribat","year":"2013","journal-title":"PLoS ONE"},{"key":"2021042501170826500_b2-0071335","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1091\/mbc.e10-06-0553","article-title":"Myosin VI and its binding partner optineurin are involved in secretory vesicle fusion at the plasma membrane","volume":"22","author":"Bond","year":"2011","journal-title":"Mol. 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