Profilin plays an important role in actin organization in all eukaryotic cells (6). Yeast profilin is an actin- and phosphatidylinositol 4,5-bisphosphate-binding protein that plays a role in the organization of the cytoskeleton (2), and resembles profilins from other organisms in molecular mass and function (7). Profilin mediates actin nucleation by an Arp2p/Arp3p-independent mechanism (8), and can sequester actin monomers, thereby reducing polymerization ability (9). Profilin also promotes rapid actin dynamics by regenerating ATP actin from ADP actin-cofilin generated during filament disassembly (10). Profilin may link signaling pathways to actin cytoskeleton organization by binding to phosphatidylinositol 4,5-bisphosphate and to polyproline stretches on several proteins (10).

Profilin plays a role in maintaining normal actin filament levels in response to shifts to high temperature. Cells lacking profilin display a greater drop in actin filament levels upon such temperature shifts, and are slower to recover to initial actin filament levels than are wild-type cells. Profilin null cells contain normal concentrations of actin filament while growing exponentially at room temperature, indicating that profilin is not essential for maintaining actin filament concentrations during steady-state growth (3).

Yeast cells can survive without detectable profilin, but such cells grow slowly, are temperature sensitive, lose the normal ellipsoidal shape of yeast cells, often become multinucleate, and generally grow much larger than wild-type cells. In addition, these cells exhibit delocalized deposition of cell wall chitin, have dramatically altered actin distributions, and exhibit abnormal bud formation, cytokinesis, and spore germination (7, 11, 12). Overexpression of profilin leads to no very obvious phenotype, but can compensate for the deleterious effects of too much actin in a profilin concentration-dependent manner (13). Mutations in the late secretory gene SEC3, and also in several other late secretory genes, are synthetically lethal with profilin mutations, suggesting a role for profilin in intracellular transport (12), and also cause defects in diploid-specific bud-site selection, indicating that the secretory pathway is especially crucial for maintaining budding polarity (14).

Profilin can be found in both the plasma membrane and cytosol. Actin is bound to the profilin localized in the cytosol. The association of profilin with the membrane is peripheral and mediated through interactions with phosphatidylinositol 4,5-bisphosphate. Depletion of plasma membrane phosphatidylinositol 4,5-bisphosphate levels results in translocation of profilin to the cytosol, suggesting that phosphoinositide metabolism plays a role in profilin localization (2).

Last updated: 2004-10-14