Related Experiment Video
Updated: Jun 3, 2025
07:20
Author Spotlight: Imaging ATG9A, a Multi-Spanning Membrane Protein
Published on: June 16, 2023
2.0K
ATG9 promotes autophagosome formation through interaction with LC3
Peiqi Xu1, Ting Zhang2, Fangfang Yu1
1Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China.
Biochemical and Biophysical Research Communications
|January 9, 2025
Summary
ATG9 protein binds to LC3, a key membrane component, facilitating its incorporation into the autophagosome during macroautophagy. This interaction is crucial for autophagosome formation and biogenesis.
Area of Science:
- Cell Biology
- Molecular Biology
Background:
- Macroautophagy is a cellular process mediated by the autophagosome, a double-membrane organelle.
- Autophagosome formation relies on autophagy-related genes, with ATG9 being a critical transmembrane protein.
- The mechanism by which ATG9 integrates into the growing autophagosome membrane remained unclear.
Purpose of the Study:
- To elucidate the molecular mechanism of ATG9 binding to the autophagosome membrane.
- To identify the interaction partners and binding sites involved in ATG9 recruitment.
Main Methods:
- Investigated the interaction between ATG9 and LC3 using biochemical assays.
- Characterized the role of ATG9's UIM motifs and LC3's UDS site in their interaction.
- Assessed the impact of disrupting the ATG9-LC3 interaction on autophagosome formation.
Main Results:
- ATG9 directly binds to LC3, an essential autophagosome membrane component.
- The interaction occurs via ATG9's Ubiquitin-Interacting Motifs (UIMs) binding to the Ubiquitin-Docks Site (UDS) on LC3.
- Disruption of the UIM-UDS interaction prevents ATG9 recruitment to the autophagosome and inhibits autophagosome formation.
Conclusions:
- A novel mechanism for ATG9 recruitment to the autophagosome membrane has been identified.
- The interaction between ATG9 and LC3 is essential for ATG9's role in autophagosome biogenesis.
- This finding provides new insights into the regulation of macroautophagy.
Related Concept Videos
01:27Autophagy
4.2K
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.2K
01:36Delivery Pathways to the Lysosome
6.1K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.1K
01:18Autophagic Cell Death
3.4K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.4K
01:38Intralumenal Vesicles and Multivesicular Bodies
3.4K
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
3.4K
01:32Export of Misfolded Proteins out of the ER
3.5K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.5K
01:33Coat Assembly and GTPases
3.5K
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.5K