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

TL;DR

The paper proposes a new mechanism for intracellular transport where cargo moves with moving microtubules, not just along them, which could impact understanding of neurological disorders.

Contribution

The novelty is the proposal of co-migration of cargo with moving microtubules as a complementary transport mechanism.

Findings

Cargo co-migration with moving microtubules may operate across cell types.

Directional microtubule movements can be generated through motor-driven sliding and cortical gliding.

This mechanism adds a layer of directional control to intracellular transport.

Abstract

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.

Directional intracellular cargo transport is traditionally attributed to motor stepping along stationary microtubule (MT) tracks. We propose a complementary mechanism of cargo co‐migration with moving MTs. This mode requires cargo–MT tethering and directed MT motion. Future investigation will offer new insights into neurodevelopmental and neurodegenerative disorders.

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