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Mol Cell. 2018 May 3;70(3):516-530.e6. doi: 10.1016/j.molcel.2018.03.026. Epub 2018 Apr 26.

Redundant and Antagonistic Roles of XTP3B and OS9 in Decoding Glycan and Non-glycan Degrons in ER-Associated Degradation.

Author information

1
Department of Biology, Stanford University, Stanford, CA 94305, USA.
2
SRI International, Menlo Park, CA 94025, USA.
3
Department of Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: kopito@stanford.edu.

Abstract

Glycoproteins engaged in unproductive folding in the ER are marked for degradation by a signal generated by progressive demannosylation of substrate N-glycans that is decoded by ER lectins, but how the two lectins, OS9 and XTP3B, contribute to non-glycosylated protein triage is unknown. We generated cell lines with homozygous deletions of both lectins individually and in combination. We found that OS9 and XTP3B redundantly promote glycoprotein degradation and stabilize the SEL1L/HRD1 dislocon complex, that XTP3B profoundly inhibits the degradation of non-glycosylated proteins, and that OS9 antagonizes this inhibition. The relative expression of OS9 and XTP3B and the distribution of glycan and non-glycan degrons within the same protein contribute to the fidelity and processivity of glycoprotein triage and, therefore, determine the fates of newly synthesized proteins in the early secretory pathway.

KEYWORDS:

ER protein quality control; ER-associated degradation; OS9; SEL1L-HRD1 complex; XTP3B; glycoprotein; lectin

PMID:
29706535
PMCID:
PMC5935522
DOI:
10.1016/j.molcel.2018.03.026
[Indexed for MEDLINE]
Free PMC Article

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