Journal
BIOCHEMICAL JOURNAL
Volume 457, Issue -, Pages 485-496Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20130155
Keywords
endoplasmic reticulum (ER); ER-degradation enhancing alpha-mannosidase I-like protein 1 (EDEM1); EDEM2; retrotranslocation; ricin
Categories
Funding
- Ministry of Science and Higher Education [N N301 473138]
- Foundation for Polish Science [HOM/12/2007]
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EDEM1 [ER (endoplasmic reticulum)-degradation-enhancing alpha-mannosidase I-like protein 1] and EDEM2 are crucial regulators of BRAD (ER-associated degradation) that extracts non-native glycoproteins from the calnexin chaperone system. Ricin is a potent plant cytotoxin composed of an A-chain (RTA) connected by a disulfide bond to a cell-binding lectin B-chain (RTB). After endocytic uptake, the toxin is transported retrogradely to the ER, where the enzymatically active RTA is translocated to the cytosol in a similar manner as misfolded ER proteins. This transport is promoted by EDEM1. In the present study we report that EDEM2 is also involved in ricin retrotranslocation out of the ER. However, the role of EDEM1 and EDEM2 in ricin transport to the cytosol seems to differ. EDEM2 promotes ricin retrotranslocation irrespectively of ER translocon accessibility; moreover, co-immunoprecipitation and pull-down studies revealed that more ricin can interact with EDEM2 in comparison with EDEM1. On the other hand, interactions of both lectins with RTA are dependent on the structure of the RTA. Thus our data display a newly discovered role for EDEM2. Moreover, analysis of the involvement of EDEM1 and EDEM2 in ricin retrotranslocation to the cytosol may provide crucial information about general mechanisms of the recognition of BRAD substrates in the ER.
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