Modulation of gelsolin function by phosphatidylinositol 4,5-bisphosphate.
The actin-binding protein gelsolin requires micromolar concentrations of calcium ions to sever actin filaments, to potentiate its binding to the end of the filament and to promote the polymerization of monomeric actin into filaments. Because transient increases in both intracellular [Ca2+] and actin polymerization accompany the cellular response to certain stimuli, it has been suggested that gelsolin regulates the reversible assembly of actin filaments that accompanies such cellular activations. But other evidence suggests that these activities do not need increased cytoplasmic [Ca2+] and that once actin-gelsolin complexes form in the presence of Ca2+ in vitro, removal of free Ca2+ causes dissociation of only one of two bound actin monomers from gelsolin and the resultant binary complexes cannot sever actin filaments. The finding that cellular gelsolin-actin complexes can be dissociated suggests that a Ca2+-independent regulation of gelsolin also occurs. Here we show that, like the dissociation of profilin-actin complexes, phosphatidylinositol 4,5-bisphosphate, which undergoes rapid turnover during cell stimulation, strongly inhibits the actin filament-severing properties of gelsolin, inhibits less strongly the nucleating ability of this protein and restores the potential for filament-severing activity to gelsolin-actin complexes.
D008841:Actin Cytoskeleton / Q000502:physiology*; D000199:Actins / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology*; D018260:Gelsolin; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008264:Macrophages; D008840:Microfilament Proteins / Q000502:physiology*; D010716:Phosphatidylinositols / Q000502:physiology*; D011485:Protein Binding; D011817:Rabbits
D000199:Actins; D002135:Calcium-Binding Proteins; D018260:Gelsolin; D046911:Macromolecular Substances; D008840:Microfilament Proteins; D010716:Phosphatidylinositols