{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T06:41:49Z","timestamp":1773729709581,"version":"3.50.1"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,8,15]]},"abstract":"<jats:p>Deletion of a single glutamate in torsinA correlates with early-onset dystonia, the most severe form of a neurological disorder characterized by uncontrollable muscle contractions. TorsinA is targeted to the ER (endoplasmic reticulum) in eukaryotic cells. We investigated the processing and membrane association of torsinA and the dystonia-associated Glu-deletion mutant (torsinA\u0394E). We found that the signal sequence of torsinA (residues 1\u201320 from the 40 amino-acid long N-terminal hydrophobic region) is cleaved in Drosophila S2 cells, as shown by the N-terminal sequencing after partial protein purification. TorsinA is not secreted from S2 cells. Consistently, sodium carbonate extraction and Triton X-114 treatment showed that torsinA is associated with the ER membrane in CHO (Chinese-hamster ovary) cells. In contrast, a variant of torsinA that contains the native signal sequence without the hydrophobic region Ile24\u2013Pro40 does not associate with the membranes in CHO cells, and a truncated torsinA without the 40 N-terminal amino acids is secreted in the S2 culture. Thus the 20-amino-acid-long hydrophobic segment in torsinA, which remains at the N-terminus after signal-peptide cleavage, is responsible for the membrane anchoring of torsinA. TorsinA\u0394E showed similar cleavage of the 20 N-terminal amino acids and membrane association properties similar to wild-type torsinA but, unlike the wild-type, torsinA\u0394E was not secreted in the S2 culture even after deletion of the membrane-anchoring segment. This indicates that the dystonia-associated mutation produces a structurally distinct, possibly misfolded, form of torsinA, which cannot be properly processed in the secretory pathway of eukaryotic cells.<\/jats:p>","DOI":"10.1042\/bj20030258","type":"journal-article","created":{"date-parts":[[2003,8,18]],"date-time":"2003-08-18T10:49:53Z","timestamp":1061203793000},"page":"117-122","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Characterization of human torsinA and its dystonia-associated mutant form"],"prefix":"10.1042","volume":"374","author":[{"given":"Zhonghua","family":"LIU","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Kansas State University, 104 Willard Hall, Manhattan, KS 66506, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"ZOLKIEWSKA","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kansas State University, 104 Willard Hall, Manhattan, KS 66506, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"ZOLKIEWSKI","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kansas State University, 104 Willard Hall, Manhattan, KS 66506, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/374\/1\/117\/711872\/bj3740117.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/374\/1\/117\/711872\/bj3740117.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T14:15:52Z","timestamp":1637590552000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/374\/1\/117\/43634\/Characterization-of-human-torsinA-and-its-dystonia"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,8,15]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,8,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj20030258","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,8,15]]}}}