Cellular motility is based on the continuous disassembly and reconstruction of the actin cytoskeleton orchestrated by numerous actin binding proteins, of which the activity is regulated in response to signal transduction. Profilins are small actin binding proteins that, in organisms, are often present as different isoforms with distinct expression patterns. Biochemical experiments demonstrated a dual activity for profilins in the regulation of dynamics of actin polymerization, but also that profilins bind proline-rich sequences and polyphospoinositides. Intriguingly, the various mammalian profilin isoforms have different preferences for these ligands. In addition other protein partners for profilin have recently been identified. The interactions of profilins with the proline-rich region of Enabled/Vasodilator-stimulated phosphoprotein (Ena/VASP) proteins, Wiskott-Aldrich syndrome protein (WASP) family members, formins and Survival of Motoneuron protein (SMN) have been demonstrated, leading to different effects on actin dynamics. The binding to the polyphosphoinositide, phosphatidylinositol 4,5-bisphosphate (PI-(4,5)-P2), inhibits profilin activity. These various types of ligand interactions suggest that profilins are involved in complex networks influencing the regulation of cellular actin dynamics, which is supported by cell biological experiments implicating profilins in a variety of functions including cell migration, neuronal development and cytokinesis. More recently a role for profilin in the nucleus has been suggested and links to pathologies have been established.
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