{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:46:43Z","timestamp":1790646403368,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,6,19]],"date-time":"2015-06-19T00:00:00Z","timestamp":1434672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH\/NINDS","award":["NS066339"],"award-info":[{"award-number":["NS066339"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Huntington's disease (<jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>) is a hereditary and devastating neurodegenerative disorder caused by a mutation in the huntingtin protein. Understanding the functions of normal and mutant huntingtin protein is the key to revealing the pathogenesis of <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> and developing therapeutic targets. Huntingtin plays an important role in vesicular and organelle trafficking. Lysosomes are dynamic organelles that integrate several degradative pathways and regulate the activity of mammalian target of rapamycin complex 1 (<jats:styled-content style=\"fixed-case\">mTORC<\/jats:styled-content>1). In the present study, we found that the perinuclear accumulation of lysosomes was increased in a cellular model of <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> derived from <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> knock\u2010in mice and primary fibroblasts from an <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> patient. This perinuclear lysosomal accumulation could be reversed when normal huntingtin was overexpressed in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> cells. When we further investigated the functional significance of the increased perinuclear lysosomal accumulation in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> cells, we demonstrated that basal <jats:styled-content style=\"fixed-case\">mTORC<\/jats:styled-content>1 activity was increased in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> cells. In addition, autophagic influx was also increased in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> cells in response to serum deprivation, which leads to premature fusion of lysosomes with autophagosomes. Taken together, our data suggest that the increased perinuclear accumulation of lysosomes may play an important role in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> pathogenesis by altering lysosomal\u2010dependent functions.<\/jats:p>","DOI":"10.1111\/ejn.12957","type":"journal-article","created":{"date-parts":[[2015,5,22]],"date-time":"2015-05-22T07:00:20Z","timestamp":1432278020000},"page":"1941-1951","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Altered lysosomal positioning affects lysosomal functions in a cellular model of Huntington's disease"],"prefix":"10.1111","volume":"42","author":[{"given":"Christine","family":"Erie","sequence":"first","affiliation":[{"name":"Department of Biomedical Science Charles E. Schmidt College of Medicine Florida Atlantic University Boca Raton FL 33431 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Sacino","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science Charles E. Schmidt College of Medicine Florida Atlantic University Boca Raton FL 33431 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Houle","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science Charles E. Schmidt College of Medicine Florida Atlantic University Boca Raton FL 33431 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science Charles E. Schmidt College of Medicine Florida Atlantic University Boca Raton FL 33431 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianning","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science Charles E. Schmidt College of Medicine Florida Atlantic University Boca Raton FL 33431 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm217"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200507002"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4405"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2009.01.005"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E10-03-0233"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.133"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.09.015"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.01.024"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02633"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.108.3.855"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1624"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/currents.RRN1211"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2008.00701.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.03.018"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.21.5720"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.04.048"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-19-07268.2000"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2204"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2009.06.008"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2528"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.11.049"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0106-08.2008"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702824200"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2005633"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl440"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.024"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3156"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2313"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81459-2"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.19.2799"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.12.007"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1870-13.2014"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-14-3"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1219"}],"container-title":["European Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fejn.12957","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejn.12957","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T09:58:51Z","timestamp":1696327131000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejn.12957"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,19]]},"references-count":34,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,8]]}},"alternative-id":["10.1111\/ejn.12957"],"URL":"https:\/\/doi.org\/10.1111\/ejn.12957","archive":["Portico"],"relation":{},"ISSN":["0953-816X","1460-9568"],"issn-type":[{"value":"0953-816X","type":"print"},{"value":"1460-9568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,19]]},"assertion":[{"value":"2015-03-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-05-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-06-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}