Mechanistic understanding of kinesin–dynein interactions on shared cargo

Determine the mechanistic basis of interactions between kinesin and dynein motors when both are attached to the same intracellular cargo in bidirectional transport, traditionally described as a tug-of-war, in order to clarify how these interactions generate the observed complexity of motor-driven intracellular transport.

Background

Bidirectional transport of intracellular cargos, including dense-core vesicles (DCVs), is often attributed to simultaneous engagement of oppositely directed motors—kinesin for anterograde and dynein for retrograde movement. A common conceptual model frames this as a tug-of-war, where motors compete to determine net cargo direction.

Despite extensive study, the detailed physical and regulatory mechanisms governing kinesin–dynein interactions on shared cargo remain unresolved. The present work focuses on a statistical model of DCV movement heterogeneity and superdiffusion rather than the molecular-level motor interplay, highlighting the need to elucidate how co-attached motors coordinate, compete, or switch activity to produce the complex transport behaviors observed in cells.

References

Interactions between kinesin and dynein motors, traditionally conceived as a “tug-of-war” between oppositely-directed motors attached to the same cargo, contribute to this complexity and are not yet fully understood.

Heterogeneous model for superdiffusive movement of dense-core vesicles in C. elegans  (2407.18237 - Gavrilova et al., 2024) in Introduction