Profilin

Profilin is a small actin-binding protein that regulates actin dynamics in eukaryotic cells. It binds monomeric actin (G-actin), sequestering it away from spontaneous nucleation, and facilitates the exchange of ADP for ATP on G-actin. In the presence of actin nucleators such as formins and other proline-rich proteins, profilin delivers ATP-actin monomers to growing barbed ends, promoting filament elongation. Profilin also binds to poly-L-proline sequences found in many actin regulators and signaling proteins, functioning as a hub that coordinates cytoskeletal remodeling with signaling pathways. It also interacts with phosphatidylinositol 4,5-bisphosphate (PIP2) at membranes, which can regulate profilin’s activity and localization by modulating its interaction with actin monomers.

In humans, the profilin family comprises several isoforms, with PFN1 and PFN2 being the best characterized. PFN1 is expressed broadly, while PFN2 has a more restricted tissue distribution (e.g., brain). The proteins are about 131–134 amino acids long, with a conserved fold that supports actin binding and proline-rich motif interactions. Profilin is essential for normal cytoskeletal dynamics and is conserved across many eukaryotes, from yeast to humans.

Biological importance and clinical relevance: Profilin participates in cell motility, endocytosis, and development. Genetic disruption can cause cytoskeletal defects and impaired signaling. Mutations in PFN1 have been linked to familial neurodegenerative conditions such as amyotrophic lateral sclerosis and related disorders, underscoring profilin’s role in neuronal structure and function. Altered profilin expression or function is observed in various cancers and brain disorders, with effects depending on cellular context.

Summary: Profilin acts as a key regulator of actin filament turnover and assembly, coordinating cytoskeletal dynamics with signaling through interactions with actin, proline-rich ligands, and membrane lipids.