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. 2018 Oct 1;29(20):2397–2409. doi: 10.1091/mbc.E18-06-0380

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© 2018 Tiengwe, Koeller, and Bangs. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.

This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.

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FIGURE 9: — ERAD model in trypanosomes. 1) Newly synthesized GPI-anchored glycoprotein enters into the calnexin cycle of de-/reglucosylation. 2) The protein fails to achieve final folding status, but the GPI forward trafficking signal is unable to overcome retention by ER quality control. 3) The calnexin cycle is broken by TbEDEM-mediated demannosylation. 4) The trimmed glycoprotein is delivered to the TbHrd1-containing retrotranslocation complex by the lectin TbOS-9. 5) Translocation occurs, presumably with concomitant ubiquitinylation by TbHrd1, but this is not certain, based on data presented here (indicated by “?”). Dimyristoylglycerol is removed by membrane-bound GPI-PLC. N-glycans are removed by cytosolic endo-β-N-acetylglucosaminidase (TbENG). 6) The substrate is extracted from the membrane by TbVCP and delivered to the proteasome for degradation.