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Updated: Oct 3, 2025

Author Spotlight: Imaging ATG9A, a Multi-Spanning Membrane Protein
Published on: June 16, 2023
The core autophagy protein ATG9A controls dynamics of cell protrusions and directed migration
Daniele Campisi1,2, Laurence Desrues1,2, Kléouforo-Paul Dembélé1,2
1Normandie University, UNIROUEN, Institut national de la santé et de la recherche médicale U1239, DC2N, Rouen, France.
Abstract:
Chemotactic migration is a fundamental cellular behavior relying on the coordinated flux of lipids and cargo proteins toward the leading edge. We found here that the core autophagy protein ATG9A plays a critical role in the chemotactic migration of several human cell lines, including highly invasive glioma cells. Depletion of ATG9A protein altered the formation of large and persistent filamentous actin (F-actin)-rich lamellipodia that normally drive directional migration. Using live-cell TIRF microscopy, we demonstrated that ATG9A-positive vesicles are targeted toward the migration front of polarized cells, where their exocytosis correlates with protrusive activity. Finally, we found that ATG9A was critical for efficient delivery of β1 integrin to the leading edge and normal adhesion dynamics. Collectively, our data uncover a new function for ATG9A protein and indicate that ATG9A-positive vesicles are mobilized during chemotactic stimulation to facilitate expansion of the lamellipodium and its anchorage to the extracellular matrix.
Insights
The autophagy protein ATG9A is crucial for cell migration, guiding vesicles to the cell front to support lamellipodia formation and adhesion dynamics in human cells.
Area of Science:
- Cell Biology
- Molecular Biology
- Autophagy Research
Background:
- Chemotactic migration is essential for cellular functions, involving coordinated movement of lipids and proteins.
- The protein ATG9A is a core component of autophagy, but its role in cell migration is not well understood.
Purpose of the Study:
- To investigate the role of ATG9A in chemotactic cell migration.
- To elucidate the mechanism by which ATG9A influences cell movement and adhesion.
Main Methods:
- Depletion of ATG9A protein in human cell lines.
- Live-cell Total Internal Reflection Fluorescence (TIRF) microscopy.
- Analysis of filamentous actin (F-actin) structures and cell adhesion dynamics.
Main Results:
- ATG9A depletion impaired the formation of F-actin-rich lamellipodia, crucial for directional migration.
- ATG9A-positive vesicles were observed moving towards the cell's leading edge, correlating with cell protrusion.
- ATG9A was essential for delivering β1 integrin to the leading edge, impacting adhesion.
Conclusions:
- ATG9A plays a novel and critical role in chemotactic cell migration.
- ATG9A-positive vesicles are mobilized during chemotaxis to promote lamellipodium expansion and extracellular matrix anchorage.
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