Profilin enhances actin growth in two ways: • Profilin binds to monomeric actin thereby occupying an actin-actin contact site; in effect, profilin sequesters actin from the pool of polymerizable actin monomers. However, profilin also catalyzes the exchange of actin-bound
ADP to
ATP thereby converting poorly polymerizing ADP-actin monomers into readily polymerizing ATP-actin monomers. On top of that, profilin has a higher affinity for ATP- than for ADP-actin monomers. Thus in a mixture of actin, profilin, and nucleotides (ADP and ATP), actin will polymerize to a certain extent, which may be estimated by the
law of mass action. • Profilin-actin complexes are fed into growing actin polymers by proteins such as
formin,
Wiskott-Aldrich syndrome protein and
Vasodilator-stimulated phosphoprotein which contain proline-rich FH1-domains. This mode of stimulated actin polymerization is much faster than unaided polymerization. Profilin is essential for this mode of polymerization because it recruits the actin monomers to the proline-rich proteins. Profilin binds some variants of
membrane phospholipids (
phosphatidylinositol (4,5)-bisphosphate and
inositol trisphosphate). The function of this interaction is the sequestration of profilin in an "inactive" form, from where it can be released by action of the enzyme
phospholipase C. Profilin negatively regulates
PI(3,4)P2 limiting recruitment of
lamellipodia to the leading edge of the cell. Profilin is one of the most abundant actin monomer binders, but proteins such as
CAP and (in mammals)
thymosin β4 have some functional overlaps with profilin. In contrast, ADF/
cofilin has some properties that antagonize profilin action. ==History of discovery==