ADF and Cofilin1 Control Actin Stress Fibers, Nuclear Integrity, and Cell Survival

Area of Science:

• Cell Biology
• Molecular Biology
• Biophysics

Background:

• Actin-severing proteins, including Actin Depolymerizing Factor (ADF) and Cofilin 1 (CFL1), are crucial for regulating actin dynamics.
• Dysregulation of actin cytoskeleton dynamics is implicated in various cellular pathologies and tissue dysfunction.
• The precise role of ADF and CFL1 in maintaining nuclear integrity and tissue homeostasis remains incompletely understood.

Purpose of the Study:

• To investigate the consequences of co-depleting ADF and CFL1 on cellular and tissue homeostasis.
• To elucidate the molecular mechanisms by which ADF and CFL1 regulate actin dynamics and nuclear integrity.
• To establish the link between actin contractility, nuclear deformation, and cell survival.

Main Methods:

• Genetic co-depletion of ADF and CFL1 in relevant model systems.
• Analysis of cell-cell adhesion, keratinocyte proliferation, and apoptosis.
• Assessment of actin stress fiber organization, focal adhesions, and membrane protrusion dynamics.
• Investigation of nuclear deformation and nuclear lamina integrity using the LINC complex.

Main Results:

• Co-depletion of ADF and CFL1 leads to loss of adult tissue homeostasis, impaired cell-cell adhesion, and hyperproliferation.
• Uncontrolled accumulation of contractile actin stress fibers and enlarged focal adhesions were observed.
• Increased intracellular acto-myosin tension resulted in nuclear deformation and disruption of the nuclear lamina via the LINC complex.
• Reduced rates of membrane protrusions were noted.

Conclusions:

• ADF and CFL1 are vital for regulating the dynamic turnover of contractile actin stress fibers.
• Proper regulation of actin stress fibers by ADF and CFL1 prevents nuclear damage from actin contractility.
• These actin-severing proteins are essential for preserving cell survival and maintaining tissue homeostasis.