Motor-Assisted Co-Migration of Intracellular Organelles and Microtubules as a Mechanism for Directed Cargo Transport

Intracellular cargo transport relies on a microtubule (MT) network and its molecular motors, dynein and kinesin. While conventional models emphasize motor-driven cargo movement along stationary MT tracks, emerging evidence suggests that dynamic movements of MTs also contribute to directional transport. We propose a model of cargo co-migration with moving MTs, exemplified by nuclear migration in developing neurons. This transport mode may operate across cell types, provided that cargo-MT tethering and directional MT movements are present. We hypothesize multiple complementary mechanisms, including motor catch-bond formation and clustering, as well as MT-associated protein-mediated anchorage. We further discuss how directional MT movements can be generated through motor-driven sliding, cortical gliding, actin-MT crosslinking, and dynamic MT instability. This coupled transport mechanism provides an additional layer of directional control that supplements motor-stepping-dependent transport. Potential experimental approaches to validate this hypothesis are discussed. Understanding MT-mediated cargo delivery could refine our current models of intracellular transport and reveal new insights into neurodevelopmental and neurodegenerative disorders.