Abstract
Motor-mediated intracellular trafficking requires motors to position cargoes at proper locations. Myosin Va (MyoVa), an actin-based motor, is a classic model for studying cargo transport. However, the molecular basis underlying cargo unloading in MyoVa-mediated transport has remained enigmatic. We have identified MICAL1, an F-actin disassembly regulator, as a binding partner of MyoVa and shown that MICAL1-MyoVa interaction is critical for localization of MyoVa at the midbody. By binding to MICAL1, MyoVa-mediated transport is terminated, resulting in vesicle unloading at the midbody for efficient cytokinesis. The MyoVa/MICAL1 complex structure reveals that MICAL1 and F-actin assembly factors, Spires, share an overlapped binding surface on MyoVa, suggesting a regulatory role of F-actin dynamics in cargo unloading. Down-regulating F-actin disassembly by a MICAL1 mutant significantly reduces MyoVa and vesicles accumulating at the midbody. Collectively, our findings demonstrate that MyoVa binds to MICAL1 at the midbody destination and triggers F-actin disassembly to unload the vesicle cargo.