{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:52:01Z","timestamp":1789411921409,"version":"build-2803163510"},"reference-count":55,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,9,30]]},"abstract":"<jats:p>Many genetic mouse models of Huntington\u2019s disease (HD) have established that mutant huntingtin (htt) accumulates in various subcellular regions to affect a variety of cellular functions, but whether and how synaptic mutant htt directly mediates HD neuropathology remains to be determined. We generated transgenic mice that selectively express mutant htt in the presynaptic terminals. Although it was not overexpressed, synaptic mutant htt caused age-dependent neurological symptoms and early death in mice as well as defects in synaptic neurotransmitter release. Mass spectrometry analysis of synaptic fractions and immunoprecipitation of synapsin-1 from HD CAG150 knockin mouse brains revealed that mutant htt binds to synapsin-1, a protein whose phosphorylation is critical for neurotransmitter release. We found that polyglutamine-expanded exon1 htt binds to the C-terminal region of synapsin-1 to reduce synapsin-1 phosphorylation. Our findings point to a critical role for synaptic htt in the neurological symptoms of HD, providing a new therapeutic target.<\/jats:p>","DOI":"10.1083\/jcb.201303146","type":"journal-article","created":{"date-parts":[[2013,9,30]],"date-time":"2013-09-30T19:10:16Z","timestamp":1380568216000},"page":"1123-1138","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Synaptic mutant huntingtin inhibits synapsin-1 phosphorylation and causes neurological symptoms"],"prefix":"10.1083","volume":"202","author":[{"given":"Qiaoqiao","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Histology and Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430032, China 1"},{"name":"Department of Human Genetics 2 and 3"},{"name":"Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322 2 and 3"},{"name":"State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100864, China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Human Genetics 2 and 3"},{"name":"Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322 2 and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingke","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Human Genetics 2 and 3"},{"name":"Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322 2 and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan-En","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Human Genetics 2 and 3"},{"name":"Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322 2 and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics 2 and 3"},{"name":"Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322 2 and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100864, China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta A.","family":"Gaertig","sequence":"additional","affiliation":[{"name":"Department of Human Genetics 2 and 3"},{"name":"Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322 2 and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan Ping","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Human Genetics 2 and 3"},{"name":"Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322 2 and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Histology and Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430032, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Human Genetics 2 and 3"},{"name":"Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322 2 and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Human Genetics 2 and 3"},{"name":"Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322 2 and 3"},{"name":"State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100864, China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2013,9,30]]},"reference":[{"key":"2023072306072515800_bib1","doi-asserted-by":"publisher","first-page":"6809","DOI":"10.1073\/pnas.120166397","article-title":"Severe deficiencies in dopamine signaling in presymptomatic Huntington\u2019s disease mice","volume":"97","author":"Bibb","year":"2000","journal-title":"Proc. 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