TBK1-mediated phosphorylation of LC3C and GABARAP-L2 controls autophagosome shedding by ATG4 protease.
In: EMBO reports, Jg. 21 (2020-01-07), Heft 1, S. e48317
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Zugriff:
Autophagy is a highly conserved catabolic process through which defective or otherwise harmful cellular components are targeted for degradation via the lysosomal route. Regulatory pathways, involving post-translational modifications such as phosphorylation, play a critical role in controlling this tightly orchestrated process. Here, we demonstrate that TBK1 regulates autophagy by phosphorylating autophagy modifiers LC3C and GABARAP-L2 on surface-exposed serine residues (LC3C S93 and S96; GABARAP-L2 S87 and S88). This phosphorylation event impedes their binding to the processing enzyme ATG4 by destabilizing the complex. Phosphorylated LC3C/GABARAP-L2 cannot be removed from liposomes by ATG4 and are thus protected from ATG4-mediated premature removal from nascent autophagosomes. This ensures a steady coat of lipidated LC3C/GABARAP-L2 throughout the early steps in autophagosome formation and aids in maintaining a unidirectional flow of the autophagosome to the lysosome. Taken together, we present a new regulatory mechanism of autophagy, which influences the conjugation and de-conjugation of LC3C and GABARAP-L2 to autophagosomes by TBK1-mediated phosphorylation.
(© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)
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TBK1-mediated phosphorylation of LC3C and GABARAP-L2 controls autophagosome shedding by ATG4 protease.
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Autor/in / Beteiligte Person: | Herhaus, L ; Bhaskara, RM ; Lystad, AH ; Gestal-Mato, U ; Covarrubias-Pinto, A ; Bonn, F ; Simonsen, A ; Hummer, G ; Dikic, I |
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Zeitschrift: | EMBO reports, Jg. 21 (2020-01-07), Heft 1, S. e48317 |
Veröffentlichung: | 2024- : [London] : Nature Publishing Group ; <i>Original Publication</i>: Oxford, UK : Published for EMBO by Oxford University Press, 2000-, 2020 |
Medientyp: | academicJournal |
ISSN: | 1469-3178 (electronic) |
DOI: | 10.15252/embr.201948317 |
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