The Molecular Adaptations of Myosin X for Bundled Actin Filament Tracks

Abstract

To properly self-organize, cells must be able to direct cargo to specific locations. Although many molecular motors are known to drive cargo transport, the address system that these motors use to move to the proper destination is poorly understood. Recently, we showed that myosin X has a preference for bundled actin filaments. This preference for bundles allows myosin X to identify filopodia, a limited population of actin filaments within the cell. To clarify the bundle selection mechanism, we performed single-molecule mechanical measurements to determine the stepping pattern on bundles. Our observed ∼18 nm stepsize is consistent with a filament-straddling mechanism, where each head of myosin X binds to a unique filament in the bundle. A dissection of the domains required for bundle selection reveals a surprising role for the myosin X tail, a region which is likely far from the bundle itself. We find that targeted insertion of a glycine-rich flexible linker within the tail abolishes bundle selectivity, suggesting that the tail adopts a rigid structure that is essential for identifying bundles.