{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:06:48Z","timestamp":1773659208951,"version":"3.50.1"},"reference-count":44,"publisher":"The Company of Biologists","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,10,15]]},"abstract":"<jats:p>In some individuals with autosomal dominant isolated growth hormone deficiency, one copy of growth hormone lacks amino acids 32-71 and is severely misfolded. We transfected COS7 cells with either wild-type human growth hormone or \u039432-71 growth hormone and investigated subcellular localization of growth hormone and other proteins. \u039432-71 growth hormone was retained in the endoplasmic reticulum, whereas wild-type hormone accumulated in the Golgi apparatus. When cells transfected with wild-type or \u039432-71 growth hormone were dually stained for growth hormone and the Golgi markers \u03b2-COP, membrin or 58K, wild-type growth hormone was colocalized with the Golgi markers, but \u03b2-COP, membrin and 58K immunoreactivity was highly dispersed or undetectable in cells expressing \u039432-71 growth hormone. Examination of \u03b1-tubulin immunostaining showed that the cytoplasmic microtubular arrangement was normal in cells expressing wild-type growth hormone, but microtubule-organizing centers were absent in nearly all cells expressing \u039432-71 growth hormone. To determine whether \u039432-71 growth hormone would alter trafficking of a plasma membrane protein, we cotransfected the cells with the thyrotropin-releasing hormone (TRH) receptor and either wild-type or \u039432-71 growth hormone. Cells expressing \u039432-71 growth hormone, unlike those expressing wild-type growth hormone, failed to show normal TRH receptor localization or binding. Expression of \u039432-71 growth hormone also disrupted the trafficking of two secretory proteins, prolactin and secreted alkaline phosphatase. \u039432-71 growth hormone only weakly elicited the unfolded protein response as indicated by induction of BiP mRNA. Pharmacological induction of the unfolded protein response partially prevented deletion mutant-induced Golgi fragmentation and partially restored normal TRH receptor trafficking. The ability of some misfolded proteins to block endoplasmic reticulum-to-Golgi traffic may explain their toxic effects on host cells and suggests possible strategies for therapeutic interventions.<\/jats:p>","DOI":"10.1242\/jcs.114.20.3685","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T00:29:13Z","timestamp":1619396953000},"page":"3685-3694","source":"Crossref","is-referenced-by-count":44,"title":["Misfolded growth hormone causes fragmentation of the Golgi apparatus and disrupts endoplasmic reticulum-to-Golgi traffic"],"prefix":"10.1242","volume":"114","author":[{"given":"Thomas K.","family":"Graves","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilpa","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscilla S.","family":"Dannies","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia M.","family":"Hinkle","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","reference":[{"key":"2021042600015903200_ARIDOR-ETAL-1999","doi-asserted-by":"crossref","unstructured":"Aridor, M., Bannykh, S. 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