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The protein quality control receptor EDEM uses a novel vesicle transport pathway to exit the ERαα
Author(s) -
Roth Jurgen,
Guhl Bruno,
Santimaria Roger,
Cormier James,
Hebert Daniel,
Zuber Christian
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a914-c
Subject(s) - calnexin , endoplasmic reticulum , endoplasmic reticulum associated protein degradation , glycoprotein , microbiology and biotechnology , vesicle , chemistry , endosome , protein folding , cytoplasm , receptor , biology , unfolded protein response , biochemistry , calreticulin , membrane
The folding state of de novo synthesized glycoproteins in the endoplasmic reticulum (ER) is monitored by the quality control machinery. Folding incompetent glycoproteins will be retained and targeted for ER‐associated degradation (ERAD). The putative mannose binding lectin EDEM recognizes terminally misfolded glycoproteins and seems to function as an ER quality control receptor. Overexpression of EDEM results in accelerated release of abberant glycoproteins from calnexin and their subsequent proteasomal degradation. However, a mechanistic insight into how EDEM assists in the degradation process is missing. We show that EDEM preferentially exists as a soluble glycoprotein and is sequestered into ER‐derived vesicles through a novel pathway not involving the canonical transitional ER‐exit sites. We find sparse immunolabeling for EDEM throughout the ER and locally concentrated in single ER cisternae. EDEM becomes sequestered in non‐coated buds randomly located along ER cisternae outside of the transitional ER elements. The buds give rise to ~90 nm non‐coated vesicles scattered in clusters throughout the cytoplasm that also contain misfolded Hong Kong variant of α‐1‐antytrypsin. Our results demonstrate the existence of a novel vesicle transport route out of the ER, which appears to represent a vesicular sorting intermediate between the recognition of misfolded glycoproteins and their degradation.