Estrogen-related receptor α decreases RHOA stability to induce orientated cell migration

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Directional cell migration is crucial for physiological and pathological processes.
• The RHO family of GTPases plays a key role in regulating cell migration.
• Precise control over RHO GTPase activity and stability is essential for directed movement.

Purpose of the Study:

• To investigate the role of estrogen-related receptor α (ERRα) in regulating cellular migration.
• To elucidate the molecular mechanism by which ERRα influences RHOA protein turnover and cell orientation.

Main Methods:

• Investigated the transcriptional regulation of TNFAIP1 by ERRα.
• Assessed the impact of ERRα inactivation on RHOA protein stability and activation.
• Analyzed cellular morphology, actin dynamics, and lamellipodium formation.
• Evaluated directional cell migration in the absence of ERRα.

Main Results:

• ERRα directly activates the expression of TNFAIP1, which encodes BACURD2.
• BACURD2 mediates RHOA protein turnover.
• Inactivation of ERRα leads to increased RHOA stability and activation.
• Absence of ERRα results in cell disorientation, altered actin networks, and impaired lamellipodium formation.
• Directional cell migration is significantly impaired without ERRα.

Conclusions:

• ERRα regulates directional cell migration through the control of RHOA protein stability.
• The ERRα-TNFAIP1-BACURD2 pathway is critical for maintaining RHOA homeostasis and enabling directed cell movement.
• Dysregulation of this pathway affects cell migration in both physiological and pathological contexts.