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Author Spotlight: Imaging ATG9A, a Multi-Spanning Membrane Protein
Published on: June 16, 2023
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Autophagic membrane delivery through ATG9.
Yuchen Feng1, Daniel J Klionsky1
1Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Cell Research
|January 11, 2017
Summary
Autophagy relies on ATG9 protein delivery. This study reveals ATG9 trafficking from the plasma membrane and Golgi involves sorting signals and specific kinase phosphorylations for proper autophagosome formation during normal conditions and starvation.
Area of Science:
- Cell Biology
- Molecular Biology
- Autophagy Research
Background:
- Macroautophagy/autophagy is a fundamental cellular process for degrading and recycling cellular components.
- The transmembrane protein ATG9 is crucial for autophagosome biogenesis, but its precise delivery mechanism remains incompletely understood.
- Understanding ATG9 trafficking is key to elucidating the initiation and expansion phases of the autophagosome.
Purpose of the Study:
- To identify the regulatory mechanisms governing ATG9 trafficking during autophagy.
- To investigate the role of specific sorting signals and post-translational modifications in ATG9 function.
- To clarify how ATG9 contributes to membrane delivery for phagophore expansion.
Main Methods:
- Utilized molecular biology techniques to analyze ATG9 trafficking pathways.
- Investigated the interaction of ATG9 with the AP1/2 adaptor complex using conserved sorting signals.
- Examined the phosphorylation of ATG9 at specific tyrosine and serine residues by SRC kinase and ULK1, respectively.
Main Results:
- Identified two conserved sorting signals on ATG9 essential for its interaction with the AP1/2 adaptor complex.
- Demonstrated that phosphorylation of ATG9 at Tyr8 by SRC kinase and Ser14 by ULK1 is critical for its function.
- Showcased that these regulatory mechanisms control ATG9 trafficking from the plasma membrane and trans-Golgi network.
Conclusions:
- A novel mechanism regulating ATG9 trafficking has been identified, involving specific sorting signals and kinase-mediated phosphorylation.
- These findings provide critical insights into how ATG9 delivers membrane to the phagophore for autophagosome formation.
- The study elucidates the functional importance of ATG9 regulation in both basal and starvation-induced autophagy.
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