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Updated: Jun 27, 2025

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The mammalian actin elongation factor ENAH/MENA contributes to autophagosome formation via its actin regulatory

Yueheng Li1,2, Yafei Zhang2,3, Menghui Wang2

  • 1Department of Pathology, School of Basic Medical Science, Fudan University, Shanghai, China.

Autophagy
|May 5, 2024
PubMed

Insights

The actin elongation factor ENAH regulates autophagy by interacting with BECN1 and influencing autophagosome formation. ENAH is crucial for cellular homeostasis and survival during starvation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Macroautophagy/autophagy is a vital catabolic process for cellular homeostasis and survival.
  • ENAH/MENA is a key actin elongation factor with a poorly understood role in cellular processes.

Purpose of the Study:

  • To investigate the role of ENAH (ENAH actin regulator) in the autophagy process.
  • To elucidate the molecular mechanisms by which ENAH influences autophagy.

Main Methods:

  • Depletion of ENAH in cancer cells.
  • Confocal microscopy to observe colocalization of ENAH with MAP1LC3/LC3 and ATG9A.
  • Analysis of ENAH domains (EVH1, EVH2, PRD) for functional interactions.
  • Assessment of actin cytoskeleton polymerization and its impact on autophagy.

Main Results:

  • ENAH depletion inhibits autophagosome formation in cancer cells.
  • ENAH colocalizes with MAP1LC3/LC3 during starvation, dependent on actin polymerization and BECN1 interaction.
  • Mammalian ATG9A forms a ring structure around ENAH-LC3 puncta, requiring actin polymerization.
  • ENAH-led actin comet tails are observed in autophagosome trafficking.

Conclusions:

  • ENAH plays a significant regulatory role in autophagy.
  • Actin cytoskeleton dynamics, regulated by ENAH, are essential for autophagosome formation and trafficking.
  • ENAH's interaction with BECN1 and its domains are critical for its function in autophagy.
Keywords:
Actin cytoskeletonBECN1ENAHEna/Vaspautophagylive cell imaging

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