Proposed role of profilin in G-actin enrichment within dendritic spines. Actin monomers are continuously transported from the dendritic shaft to the spine head, mainly by profilin (1). Profilin facilitates the delivery of ATP-actin to the barbed ends of F-actin, providing the monomer supply for Arp2/3-mediated nucleation or formin-dependent filament elongation (2). ADP-actin dissociating from the pointed end of F-actin is bound by profilin and converted to ATP-actin, providing a diffusible pool of actin monomers (orange shading). G-actin, possibly via profilin or other, yet unknown proteins, can be immobilized by PIP₃ in the plasma membrane (3), which is generated from PIP₂ by PI3K. PIP₃ is hydrolyzed by PTEN back to PIP₂. Profilin can bind directly to PIP₂ (4) and PIP₃ (5), as well, but phosphoinositide binding competes with actin binding and leads to the release of G-actin. Elevated synaptic activity (depicted by red arrows) facilitates profilin transport to the spine and activates PI3K, leading to an increase in the immobile pool of G-actin (pink shading).