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ERRα coordinates actin and focal adhesion dynamics.

Violaine Tribollet1, Catherine Cerutti1, Alain Géloën2

  • 1Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Claude Bernard Lyon 1, CNRS UMR5242, Ecole Normale Supérieure de Lyon, 69007, Lyon, France.

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Summary
This summary is machine-generated.

Oestrogen-related receptor α (ERRα) coordinates cell migration by regulating actin dynamics and focal adhesions. ERRα controls actin polymerization via the RhoA pathway and cell adhesion via MAP4K4.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cell migration is crucial for development and disease, relying on actin cytoskeleton and focal adhesion dynamics.
  • The precise coordination of these processes is not fully understood.
  • Oestrogen-related receptor α (ERRα) was previously identified as a key regulator of cell migration.

Purpose of the Study:

  • To elucidate the mechanisms by which ERRα regulates cell migration.
  • To investigate the role of ERRα in actin cytoskeleton organization and focal adhesion dynamics.
  • To identify the specific pathways controlled by ERRα in these processes.

Main Methods:

  • ERRα depletion using siRNA.
  • Analysis of actin filament organization and cofilin activity.
  • Assessment of cell adhesion and focal adhesion formation/turnover.
  • Pharmacological inhibition of the RhoA-ROCK-LIMK-cofilin pathway.
  • Investigation of MAP4K4 as a direct target of ERRα.

Main Results:

  • Loss of ERRα resulted in abnormal actin accumulation and increased inactive cofilin.
  • ERRα depletion led to decreased cell adhesion and impaired focal adhesion dynamics.
  • Inhibition of the RhoA pathway rescued actin defects but not adhesion defects.
  • MAP4K4 was identified as a direct target of ERRα, and its inhibition rescued adhesion and focal adhesion defects in ERRα-depleted cells.

Conclusions:

  • ERRα is essential for coordinating actin dynamics and focal adhesion turnover during cell migration.
  • ERRα regulates actin polymerization through the RhoA-ROCK-LIMK-cofilin pathway.
  • ERRα controls cell adhesion and focal adhesion formation via direct regulation of MAP4K4.
  • These findings reveal independent roles for ERRα in regulating distinct but coordinated cellular processes vital for migration.