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EDEM1 recognition and delivery of misfolded proteins to the SEL1L-containing ERAD complex
Molecular Cell (2009)
  • Daniel Hebert, University of Massachusetts - Amherst
  • J. C Sunryd
  • T. Tamura
  • J. H Cormier

Terminally misfolded or unassembled secretory proteins are retained in the endoplasmic reticulum (ER) and subsequently cleared by the ER-associated degradation (ERAD) pathway. The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however, the mechanisms of substrate recognition and sorting to the ERAD pathway are poorly defined. EDEM1 (ER degradation-enhancing alpha-mannosidase-like 1 protein) has been proposed to play a role in ERAD substrate signaling or recognition. We show that EDEM1 specifically binds nonnative proteins in a glycan-independent manner. Inhibition of mannosidase activity with kifunensine or disruption of the EDEM1 mannosidase-like domain by mutation had no effect on EDEM1 substrate binding but diminished its association with the ER membrane adaptor protein SEL1L. These results support a model whereby EDEM1 binds nonnative proteins and uses its mannosidase-like domain to target aberrant proteins to the ER membrane dislocation and ubiquitination complex containing SEL1L.

Publication Date
June, 2009
Publisher Statement
doi: 10.1016/j.molcel.2009.05.018
Citation Information
Daniel Hebert, J. C Sunryd, T. Tamura and J. H Cormier. "EDEM1 recognition and delivery of misfolded proteins to the SEL1L-containing ERAD complex" Molecular Cell Vol. 34 Iss. 5 (2009)
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