Profilin and formin constitute a pacemaker system for robust actin filament growth

Area of Science:

• Cell Biology
• Biochemistry
• Biophysics

Background:

• The actin cytoskeleton is crucial for cellular functions like morphogenesis and motility.
• Controlling actin filament growth speed is essential for functional actin networks.
• The mechanisms regulating actin assembly at physiological subunit concentrations remain unclear.

Purpose of the Study:

• To investigate the regulation of mammalian actin filament assembly at physiological profilin-actin concentrations.
• To elucidate the roles of profilin and formins in controlling actin filament elongation rates.
• To understand how cells achieve robust actin growth rates despite variable subunit availability.

Main Methods:

• Reconstitution of mammalian non-muscle actin filament assembly in vitro.
• Utilizing physiological concentrations of profilin-actin.
• Investigating the influence of profilin dissociation and formin activity on filament elongation.

Main Results:

• Actin filament elongation speed is limited by profilin dissociation from the filament end.
• Filament growth rate becomes insensitive to soluble actin subunit concentration under these conditions.
• Formin actin polymerases promote profilin release, even at saturating profilin-actin levels.
• Mammalian cells operate at the growth limit imposed by profilin and formin synergy.

Conclusions:

• Profilin and formin synergy ensures robust actin filament elongation rates.
• This mechanism provides resilience to changes in soluble actin subunit concentration.
• The findings reveal a key regulatory strategy for actin cytoskeleton dynamics in cells.