Rxivist logo

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

By Lina Herhaus, Ramachandra M. Bhaskara, Alf HÃ¥kon Lystad, Anne Simonsen, Gerhard Hummer, Ivan Dikic

Posted 10 May 2019
bioRxiv DOI: 10.1101/634519 (published DOI: 10.15252/embr.201948317)

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 de-stabilizing 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.

Download data

  • Downloaded 805 times
  • Download rankings, all-time:
    • Site-wide: 36,563
    • In biochemistry: 895
  • Year to date:
    • Site-wide: 127,161
  • Since beginning of last month:
    • Site-wide: 140,514

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

News