Influence of the effector peptide of MARCKS-related protein on actin polymerization: a kinetic analysis

The members of the MARCKS protein family, MARCKS (an acronym for myristoyla ted alanine-rich C kinase substrate) and MARCKS-related protein (MRP), inte ract with membranes, protein kinase C, and calmodulin via their effector do main, a highly basic segment composed of 24-25 amino acid residues. This do main is also involved in the interaction between MARCKS/MRP and actin. In t his article we show that a peptide corresponding to the effector domain of MRP, the effector peptide, strongly influences the dynamics of actin polyme rization. Depending on the stoichiometric ratio of effector peptide to acti n the peptide either accelerates or retards the actin polymerization proces s, which takes place in the presence of near-physiological salt concentrati ons. A model is developed in which this phenomenon is explained by two inde pendent nucleation processes involving free actin monomers and peptide-boun d actin monomers, respectively. As a control, a possible regulatory mechani sm has been investigated: we show that calmodulin inhibits the actin polyme rizing activity of the MRP effector peptide, thereby validating our model a pproach. (C) 2000 Elsevier Science B.V. All rights reserved.