{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:37:06Z","timestamp":1791275826883,"version":"4.1.0"},"reference-count":38,"publisher":"American Society for Cell Biology (ASCB)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2016,4,15]]},"abstract":"<jats:p>Activation of the unfolded protein response (UPR) can be either adaptive or pathological. We term the pathological UPR that causes fatty liver disease a \u201cstressed UPR.\u201d Here we investigate the mechanism of stressed UPR activation in zebrafish bearing a mutation in the trappc11 gene, which encodes a component of the transport protein particle (TRAPP) complex. trappc11 mutants are characterized by secretory pathway defects, reflecting disruption of the TRAPP complex. In addition, we uncover a defect in protein glycosylation in trappc11 mutants that is associated with reduced levels of lipid-linked oligosaccharides (LLOs) and compensatory up-regulation of genes in the terpenoid biosynthetic pathway that produces the LLO anchor dolichol. Treating wild-type larvae with terpenoid or LLO synthesis inhibitors phenocopies the stressed UPR seen in trappc11 mutants and is synthetically lethal with trappc11 mutation. We propose that reduced LLO level causing hypoglycosylation is a mechanism of stressed UPR induction in trappc11 mutants. Of importance, in human cells, depletion of TRAPPC11, but not other TRAPP components, causes protein hypoglycosylation, and lipid droplets accumulate in fibroblasts from patients with the TRAPPC11 mutation. These data point to a previously unanticipated and conserved role for TRAPPC11 in LLO biosynthesis and protein glycosylation in addition to its established function in vesicle trafficking.<\/jats:p>","DOI":"10.1091\/mbc.e15-08-0557","type":"journal-article","created":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T23:36:32Z","timestamp":1456356992000},"page":"1220-1234","source":"Crossref","is-referenced-by-count":44,"title":["<i>trappc11<\/i>\n                    is required for protein glycosylation in zebrafish and humans"],"prefix":"10.1091","volume":"27","author":[{"given":"Charles","family":"DeRossi","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029"},{"name":"Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 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