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  TBK1-mediated phosphorylation of LC3C and GABARAP-L2 controls autophagosome shedding by ATG4 protease

Herhaus, L., Bhaskara, R., Lystad, A. H., Gestal-Mato, U., Covarrubias-Pinto, A., Bonn, F., et al. (2019). TBK1-mediated phosphorylation of LC3C and GABARAP-L2 controls autophagosome shedding by ATG4 protease. EMBO Reports, e48317. doi:10.15252/embr.201948317.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-1A68-A Version Permalink: http://hdl.handle.net/21.11116/0000-0005-1A69-9
Genre: Journal Article

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 Creators:
Herhaus, Lina1, Author
Bhaskara, Ramachandra2, Author              
Lystad, Alf Håkon3, Author
Gestal-Mato, Uxía1, Author
Covarrubias-Pinto, Adriana1, Author
Bonn, Florian1, Author
Simonsen, Anne3, Author
Hummer, Gerhard2, 4, Author              
Đikić, Ivan1, 5, Author              
Affiliations:
1Institute of Biochemistry II, School of Medicine, Goethe University, Frankfurt am Main, Germany, ou_persistent22              
2Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society, ou_2068292              
3Department of Molecular Medicine, Faculty of Medicine, Institute of Basic Medical Sciences and Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, University of Oslo, Oslo, Norway, ou_persistent22              
4Institute for Biophysics, Goethe University, Frankfurt am Main, Germany, ou_persistent22              
5Max Planck Fellow Group ER remodelling Group, Prof. Ivan Đikić, Max Planck Institute of Biophysics, Max Planck Society, ou_3004983              

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Free keywords: ATG4, ATG8, autophagy, phosphorylation, TBK1
 Abstract: 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.

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Language(s): eng - English
 Dates: 2019-10-082019-04-182019-10-152019-11-11
 Publication Status: Published online
 Pages: 20
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.15252/embr.201948317
BibTex Citekey: herhaus_tbk1-mediated_2019
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Title: EMBO Reports
  Other : EMBO Rep.
Source Genre: Journal
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Publ. Info: Oxford, UK : Published for EMBO by Oxford University Press
Pages: - Volume / Issue: - Sequence Number: e48317 Start / End Page: - Identifier: ISSN: 1469-221X
CoNE: https://pure.mpg.de/cone/journals/resource/110978984569661