Unconventional roles of nonlipidated LC3 in ERAD tuning and coronavirus infection
Volume 8, Issue 10
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Pages 1534 - 1536http://dx.doi.org/10.4161/auto.21229
: EDEM1, EDEMosomes, ERAD, ERAD tuning, ERAD tuning vesicles, LC3-I, SEL1L, autophagy, coronaviruses, endoplasmic reticulum, protein folding, protein quality control, proteostasis
Authors: Riccardo Bernasconi, Julia Noack and Maurizio Molinari View affiliations
Secretory and membrane proteins attain their native structure in the endoplasmic reticulum (ER). Folding-defective polypeptides are selected for degradation by processes collectively defined as ER-associated degradation (ERAD). Enhanced ERAD activity may interfere with protein biogenesis by inappropriately targeting not-yet-native protein folding intermediates for disposal. The regulation of ERAD is therefore crucial to maintain cellular proteostasis. At steady-state, select ERAD regulators are constitutively removed from the ER in a series of processes collectively defined as ERAD tuning. This sets the ERAD activity at levels that do not interfere with completion of ongoing folding programs. Our latest work highlights a crucial, autophagy-independent role of nonlipidated LC3 (LC3-I) as part of a membrane-bound receptor that insures the vesicle-mediated clearance of at least two ERAD regulators from the ER, EDEM1 and OS9. This pathway is hijacked by coronaviruses (CoV), and silencing of LC3 substantially inhibits viral replication.
Autophagic Punctum to:
R Bernasconi, C Galli, J Noack, S Bianchi, CAM de Haan, F Reggiori, et al. Role of the SEL1L:LC3-I complex as an ERAD tuning receptor in the mammalian ER. Mol Cell 2012; 46: 809-19
PMID: 22633958 DOI: 10.1016/j.molcel.2012.04.017
Received: June 7, 2012; Accepted: June 22, 2012; Published Online: August 16, 2012
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