Cargo-Mediated Regulation of Collective Myosin VI Motility

Abstract

Cargo transport by motor proteins organizes the cell interior. Although structure and mechanics of individual motors has been extensively studied, the regulation of motility by the cargo interface remains poorly understood. Cargo-mediated regulation occurs through cargo adapter proteins which target motors to specific cargoes and regulate motor activation and processive motility via motor dimerization. Native cellular cargoes are driven by collective motility of multiple motors bound to cargo adapter complexes. Also, cell biological and biochemical studies reveal that motor-cargo interaction is highly dynamic. Hence, it becomes imperative to understand the effect of cargo-mediated regulation on collective motility which incorporates the dynamic nature of motor-cargo interactions. Here, we report “biomimetic cargo interfaces” using DNA scaffolds to pattern myosin VI cargo-adapter complexes that enable motor turnover and tune collective myosin motility. Furthermore, using a genetically encoded myosin VI FRET biosensor we monitor structural rearrangements in the motor in real time upon effector (cargo adapter and calcium) binding both in vitro and in live cells. Our results provide novel insights into collective motor function and its regulation through dynamic modulation of motor-cargo adapter interaction.