Modulation of the mechano-chemical properties of myosin V by drebrin-E

► Myosin V lands on drebrin-decorated actin filaments with a lower frequency. ► Drebrin decreases the run length of myosin V but does not affect its velocity. ► The decoration of actin with drebrin increases load-sensitivity of the myosin V stepping. ► The main effect of drebrin is the delay of the attachment of myosin’s V leading head. The regulation of actin filament networks by various proteins has essential roles in the growth cone dynamics. In this study we focused on the actin–myosin interaction which has been suggested to be an important player in the neurite extension. We examined in vitro how the decoration of actin filaments with a side-binding protein, drebrin-E, affects the motile properties of an intracellular transporter myosin V. Single myosin V molecules landed on the drebrin-E-decorated actin filaments with a lower frequency and ran over shorter distances; however, their velocities were normal. Furthermore, the analysis of the movement of myosin V molecules in the optical trap revealed that the decoration of actin filaments with drebrin-E markedly increased the load-sensitivity of the myosin V stepping. These results are attributable to the delay in the attachment of the motor’s leading head (ADP·P i state) to actin, induced by the competitive binding of drebrin-E to actin, whereas the rate of ADP release from the trailing head (the rate-limiting step in the ATPase cycle of myosin V) is unaffected. Our study indicates that, in addition to the regulation of binding affinity of myosin V, drebrin-E also modulates the chemo-mechanical coupling in the motile myosin V molecules, presumably affecting the movement of the growth cone.