Unconventional roles of nonlipidated LC3 in ERAD tuning and coronavirus infection.
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.
Institute for Research in Biomedicine, Bellinzona, Switzerland.
Riccardo
R
Bernasconi
Julia
J
Noack
Maurizio
M
Molinari
D000818:Animals; D018352:Coronavirus Infections / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D060746:Endoplasmic Reticulum-Associated Degradation; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008954:Models, Biological; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding
D008055:Lipids; D008869:Microtubule-Associated Proteins; D010455:Peptides