Profilin is an actin-binding protein involved in the dynamic turnover and reconstruction of the actin cytoskeleton. It is found in all eukaryotic organisms in most cells. Profilin is important for spatially and temporally controlled growth of actin microfilaments, which is an essential process in cellular locomotion and cell shape changes. This restructuring of the actin cytoskeleton is essential for processes such as organ development, wound healing, and the hunting down of infectious intruders by cells of the immune system. Profilin also binds sequences rich in the amino acidproline in diverse proteins. While most profilin in the cell is bound to actin, profilins have over 50 different binding partners. Many of those are related to actin regulation, but profilin also seems to be involved in activities in the nucleus such as mRNAsplicing. Profilin binds some variants of membrane phospholipids. 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 is the major allergen present in birch, grass, and other pollen. It is essential to host cell invasion by Toxoplasma gondii. Toxoplasma profilin is the specific pathogen-associated molecular pattern of TLRs 5, 11, and 12.
Profilin sources and distribution
Profilins are proteins of molecular weights of roughly 14–19 kDa. They are present as single genes in yeast, insects, and worms, and as multiple genes in many other organisms including plants. In mammalian cells, four profilin isoforms have been discovered; profilin-I is expressed in most tissues while profilin-II is predominant in brain and kidney. Asgard archaea also use profilins.
Profilin in the regulation of actin dynamics
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, 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, WASP and VASP. 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 also negatively regulates PIP2 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 thymosin β4 have some functional overlaps with profilin. In contrast, ADF/cofilin has some properties that antagonize profilin action.
History of profilin discovery
Profilin was first described by Lars Carlsson in the lab of Uno Lindberg and co-workers in the early 1970s as the first actin monomer binding protein. It followed the realization that not only muscle, but also non-muscle cells, contained high concentrations of actin, albeit in part in an unpolymerized form. Profilin was then believed to sequester actin monomers, and release them upon a signal to make them accessible for fast actin polymer growth.
