HOOK3 is a scaffold for the opposite-polarity microtubule-based motors cytoplasmic dynein and KIF1C

The unidirectional and opposite-polarity microtubule-based motors, dynein and kinesin, drive long-distance intracellular cargo transport. Cellular observations support the existence of mechanisms to couple opposite polarity motors: in cells some cargos rapidly switch directions and kinesin motors can be used to localize dynein. We recently identified an interaction between the cytoplasmic dynein-1 activating adaptor HOOK3 and the kinesin-3 KIF1C. Here we show that KIF1C and dynein/dynactin can exist in a single complex scaffolded by HOOK3. Full-length HOOK3 binds to and activates dynein/dynactin motility. HOOK3 also binds to a short region in the “tail” of KIF1C, but unlike dynein/dynactin, this interaction does not affect the processive motility of KIF1C. HOOK3 scaffolding allows dynein to transport KIF1C towards the microtubule minus end, and KIF1C to transport dynein towards the microtubule plus end. We propose that linking dynein and kinesin motors by dynein activating adaptors may be a general mechanism to regulate bidirectional motility.