Capacity of human serum to depolymerize actin filaments.
Human blood depolymerizes filamentous (F-)actin. The interaction of actin filaments and monomers with human serum was studied by following the kinetics and extent of the depolymerization of pyrene-labeled F-actin and by analysis of serum proteins adhering to immobilized actin monomers. In physiologic Ca2+ concentrations, the depolymerization of F-actin proceeds in two stages: a rapid phase, attributed to direct severing of filaments by plasma gelsolin, and a slow phase attributed to the binding of actin monomers to vitamin D-binding protein (DBP). Without Ca2+, only the slow phase is observed. Human serum can completely depolymerize 10 to 18 mumol/L of actin, of which approximately 5 mumol/L occurs rapidly. Depolymerization can be accounted for by the normal serum concentrations of gelsolin and DBP. Fibrin(ogen) and fibronectin, which bind actin in vitro, do not contribute to the kinetics or extent of its depolymerization. Affinity chromatography and functional assays for the presence of gelsolin-actin complexes show that addition of G-actin to serum results in preferential formation of actin-DBP complexes, but that addition of F-actin to serum produces both gelsolin-actin complexes and DBP-actin complexes. The distinctive binding of actin monomers and polymers to these two serum proteins suggests a means by which their coordinated actions are maximized in vivo, from the standpoint of depolymerizing filaments and clearing monomers from the circulation.
D000199:Actins / Q000145:classification / Q000378:metabolism*; D001667:Binding, Competitive; D001790:Blood Physiological Phenomena; D002118:Calcium / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D018260:Gelsolin; D006801:Humans; D007700:Kinetics; D008840:Microfilament Proteins / Q000494:pharmacology; D009994:Osmolar Concentration; D011108:Polymers / Q000378:metabolism*; D014809:Vitamin D-Binding Protein / Q000378:metabolism / Q000494:pharmacology
D000199:Actins; D002135:Calcium-Binding Proteins; D018260:Gelsolin; D008840:Microfilament Proteins; D011108:Polymers; D014809:Vitamin D-Binding Protein; D002118:Calcium