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

**Authors:** Chuying Zhou, Mineko Kengaku

PMC · DOI: 10.1002/bies.70127 · 2026-03-25

## 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.

## Key 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.

## Linked entities

- **Proteins:** Dhc64C (Dynein heavy chain 64C), Khc (Kinesin heavy chain)

## Full-text entities

- **Genes:** betaTub60D (beta-Tubulin at 60D) [NCBI Gene 37888] {aka 143391_i_at, 3t, B3t, BETA 60D, CG3401, D.m.BETA-60D}, Arf6 (ADP ribosylation factor 6) [NCBI Gene 36699] {aka AFR51F, ARF3, ARFIII, Arf3, Arf51F, Arf51f}, Rab10 (Rab10) [NCBI Gene 33025] {aka AAF50924, CG17060, DRAB10, DRab10, DmRab10, Dmel\CG17060}, Rab7 (Rab7) [NCBI Gene 42841] {aka AAF56218, CG5915, DRAB7, DRab7, Dm Rab7, DmRab7}, Myo61F (Myosin 61F) [NCBI Gene 38153] {aka CG9155, Dm IB, DmIB, Dmel\CG9155, DroMIB, IB}, Klp64D (Kinesin-like protein at 64D) [NCBI Gene 38611] {aka CG10642, DmKlp64D, Dmel\CG10642, KIF 3A, KIF3A, KLP4}, Stim (Stromal interaction molecule) [NCBI Gene 32556] {aka C-Stim, CG9126, D-STIM, D-Stim, Dmel\CG9126, STIM1}, Lis-1 (Lissencephaly-1) [NCBI Gene 36791] {aka CG8440, D-Lis1, DLIS-1, DLIS1, DLis-1, DLis1}, Khc-73 (Kinesin heavy chain 73) [NCBI Gene 36718] {aka CG8183, DmKIN73, DmKin73, DmKlp73, Dmel\CG8183, KIF 13A}, DCTN1-p150 (Dynactin 1, p150 subunit) [NCBI Gene 39536] {aka CG9206, DCTN, DCTN-P, DCTN1, DYNA_DROME, Dctn 1-p150}, kst (karst) [NCBI Gene 38418] {aka CG12008, Dmel\CG12008, Karst, Spec-beta[[H]], beta-Spectrin, betaH}, Apc (APC-like) [NCBI Gene 44642] {aka APC1, Apc1, CG1451, D-APC, D-APC1, DAPC}, Act79B (Actin 79B) [NCBI Gene 40444] {aka 143060_f_at, ACT4, Actin, ArpF, CG7478, D}, Dhc64C (Dynein heavy chain 64C) [NCBI Gene 38580] {aka CD, CG7507, Cdhc, DHC, DHC1, DYHC}, Khc (Kinesin heavy chain) [NCBI Gene 36810] {aka 2R6, CG7765, DK, DKH, Dm KHC, DmK}, Eb1 (Eb1) [NCBI Gene 35584] {aka BcDNA.LD08743, BcDNA:LD08743, CG3265, Dm EB1, DmEB1, Dmel\CG3265}, Aplip1 (APPL-interacting protein 1) [NCBI Gene 53472] {aka Aplip, Aplip-1, CG1200, Dmel\CG1200, E(Khc)ek4, EK4}, feo (fascetto) [NCBI Gene 32015] {aka CG11207, Dmel\CG11207, EA86, Feo1, PRC1, Q54}
- **Diseases:** Alzheimer's disease (MESH:D000544), ALS (MESH:D000690), nerve damage (MESH:D000080902), neurodevelopmental and neurodegenerative diseases (MESH:D019636)
- **Chemicals:** GTP (MESH:D006160), ATP (MESH:D000255), Ca2+ (-), calcium (MESH:D002118), lipid (MESH:D008055), ADP (MESH:D000244)
- **Species:** Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Homo sapiens (human, species) [taxon 9606], Drosophila melanogaster (fruit fly, species) [taxon 7227]
- **Cell lines:** S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232)

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13015778/full.md

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Source: https://tomesphere.com/paper/PMC13015778