{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T13:55:48Z","timestamp":1760622948985},"reference-count":47,"publisher":"American Society for Cell Biology (ASCB)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2015,6,15]]},"abstract":"<jats:p>Cholera toxin (CT) intoxicates cells by trafficking from the cell surface to the endoplasmic reticulum (ER), where the catalytic CTA1 subunit hijacks components of the ER-associated degradation (ERAD) machinery to retrotranslocate to the cytosol and induce toxicity. In the ER, CT targets to the ERAD machinery composed of the E3 ubiquitin ligase Hrd1-Sel1L complex, in part via the activity of the Sel1L-binding partner ERdj5. This J protein stimulates BiP's ATPase activity, allowing BiP to capture the toxin. Presumably, toxin release from BiP must occur before retrotranslocation. Here, using loss-and gain-of-function approaches coupled with binding studies, we demonstrate that the ER-resident nucleotide exchange factors (NEFs) Grp170 and Sil1 induce CT release from BiP in order to promote toxin retrotranslocation. In addition, we find that after NEF-dependent release from BiP, the toxin is transferred to protein disulfide isomerase; this ER redox chaperone is known to unfold CTA1, which allows the toxin to cross the Hrd1-Sel1L complex. Our data thus identify two NEFs that trigger toxin release from BiP to enable successful retrotranslocation and clarify the fate of the toxin after it disengages from BiP.<\/jats:p>","DOI":"10.1091\/mbc.e15-01-0014","type":"journal-article","created":{"date-parts":[[2015,4,16]],"date-time":"2015-04-16T02:31:42Z","timestamp":1429151502000},"page":"2181-2189","source":"Crossref","is-referenced-by-count":22,"title":["The nucleotide exchange factors Grp170 and Sil1 induce cholera toxin release from BiP to enable retrotranslocation"],"prefix":"10.1091","volume":"26","author":[{"given":"Jeffrey M.","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48103"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takamasa","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan Medical School, Ann 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