Profilin prevents uncontrolled actin nucleation but channels actin monomers into productive, barbed-end elongation, especially in collaboration with nucleators like Formins — essentially acting as a gatekeeper and supplier for actin polymerization.
1. Binding to actin monomers
- Profilin binds actin monomers (G-actin) in a 1:1 complex, specifically at the barbed-end side of actin, preventing spontaneous nucleation.
- Because of this, profilin–actin complexes cannot nucleate new filaments on their own → this is the inhibitory aspect.
2. Promoting barbed-end elongation
- However, profilin–actin complexes can still be added to the barbed ends of existing filaments (but not the pointed ends).
- This accelerates elongation when barbed ends are available.
- The bound profilin dissociates upon incorporation, so actin remains in the filament.
3. Nucleotide exchange activity
- Profilin also acts as a nucleotide exchange factor for actin.
- It promotes the replacement of ADP with ATP/ADP+Pi in actin monomers.
- Since ATP-actin is the preferred substrate for polymerization, this increases the pool of polymerization-competent actin.
4. Interaction with pro-polymerization factors
- Profilin binds to poly-L-proline motifs in proteins like formins and Ena/VASP.
- These proteins nucleate and elongate filaments, and profilin delivers actin monomers directly to them.
- This creates a targeted, efficient pipeline of actin monomers into growing filaments.