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Updated: Aug 25, 2025

Author Spotlight: Imaging ATG9A, a Multi-Spanning Membrane Protein
Published on: June 16, 2023
Development of new tools to study membrane-anchored mammalian Atg8 proteins
Sang-Won Park1, Pureum Jeon2, Akinori Yamasaki3
1Department of Vector Entomology, College of Ecology and Environment, Kyungpook National University, Sangju, Korea.
Abbreviations:
A:C autophagic membrane:cytosol; ALS amyotrophic lateral sclerosis; ATG4 autophagy related 4; Atg8 autophagy related 8; BafA1 bafilomycin A1; BNIP3L/Nix BCL2 interacting protein 3 like; CALCOCO2/NDP52 calcium binding and coiled-coil domain 2; EBSS Earle's balanced salt solution; GABARAP GABA type A receptor-associated protein; GST glutathione S transferase; HKO hexa knockout; Kd dissociation constant; LIR LC3-interacting region; MAP1LC3/LC3 microtubule associated protein 1 light chain 3; NLS nuclear localization signal/sequence; PE phosphatidylethanolamine; SpHfl1 Schizosaccharomyces pombeorganic solute transmembrane transporter; SQSTM1/p62 SQSTM1/p62; TARDBP/TDP-43 TAR DNA binding protein; TKO triple knockout.
Insights
Autophagy receptor CALCOCO2/NDP52 binds to the autophagic membrane and cytosol, facilitating cargo recognition. This process is crucial for selective autophagic degradation, particularly in conditions like amyotrophic lateral sclerosis (ALS).
Area of Science:
- Cell Biology
- Molecular Biology
- Neuroscience
Background:
- Selective autophagy is a critical cellular process for degrading specific cargo, including damaged organelles and protein aggregates.
- Autophagy receptors play a key role in bridging cargo to the autophagosome machinery.
- Dysfunctional autophagy is implicated in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS).
Purpose of the Study:
- To investigate the interaction of the autophagy receptor CALCOCO2/NDP52 with the autophagic membrane and cytosol.
- To elucidate the role of CALCOCO2/NDP52 in selective autophagic cargo recognition and degradation.
- To explore the relevance of CALCOCO2/NDP52 function in the context of ALS.
Main Methods:
- Biochemical assays to study protein-protein interactions.
- Cellular imaging techniques to visualize autophagosome formation and cargo engulfment.
- Genetic manipulation (knockout strains) to assess the function of key autophagy proteins.
Main Results:
- CALCOCO2/NDP52 directly binds to the autophagic membrane and is present in the cytosol.
- CALCOCO2/NDP52 facilitates the recognition and engulfment of specific cargo into autophagosomes.
- Impaired CALCOCO2/NDP52 function affects autophagic flux and is linked to ALS-associated protein aggregation.
Conclusions:
- CALCOCO2/NDP52 is a key mediator of selective autophagy, essential for cargo recognition and autophagosome formation.
- The findings highlight the importance of CALCOCO2/NDP52 in maintaining cellular homeostasis and its potential role in ALS pathogenesis.
- Targeting CALCOCO2/NDP52 function may offer therapeutic strategies for neurodegenerative diseases.
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