Thursday, February 19, 2026
No menu items!
HomeNatureRoles of microtubules and LIS1 in dynein transport machinery assembly

Roles of microtubules and LIS1 in dynein transport machinery assembly

  • McKenney, R. J., Huynh, W., Tanenbaum, M. E., Bhabha, G. & Vale, R. D. Activation of cytoplasmic dynein motility by dynactin-cargo adapter complexes. Science 345, 337–341 (2014).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Reck-Peterson, S. L., Redwine, W. B., Vale, R. D. & Carter, A. P. The cytoplasmic dynein transport machinery and its many cargoes. Nat. Rev. Mol. Cell Biol. 19, 382–398 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, K. et al. Cryo-EM reveals how human cytoplasmic dynein is auto-inhibited and activated. Cell 169, 1303–1314 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schlager, M. A., Hoang, H. T., Urnavicius, L., Bullock, S. L. & Carter, A. P. In vitro reconstitution of a highly processive recombinant human dynein complex. EMBO J. 33, 1855–1868 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Urnavicius, L. et al. Cryo-EM shows how dynactin recruits two dyneins for faster movement. Nature 554, 202–206 (2018).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Splinter, D. et al. BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures. Mol. Biol. Cell 23, 4226–4241 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Grotjahn, D. A. et al. Cryo-electron tomography reveals that dynactin recruits a team of dyneins for processive motility. Nat. Struct. Mol. Biol. 25, 203–207 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chaaban, S. & Carter, A. P. Structure of dynein–dynactin on microtubules shows tandem adaptor binding. Nature 610, 212–216 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Singh, K. et al. Molecular mechanism of dynein-dynactin complex assembly by LIS1. Science 383, eadk8544 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cason, S. E. et al. Sequential dynein effectors regulate axonal autophagosome motility in a maturation-dependent pathway. J. Cell Biol. https://doi.org/10.1083/jcb.202010179 (2021).

  • Burute, M. & Kapitein, L. C. Cellular logistics: unraveling the interplay between microtubule organization and intracellular transport. Annu. Rev. Cell Dev. Biol. 35, 29–54 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Urnavicius, L. et al. The structure of the dynactin complex and its interaction with dynein. Science 347, 1441–1446 (2015).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chowdhury, S., Ketcham, S. A., Schroer, T. A. & Lander, G. C. Structural organization of the dynein–dynactin complex bound to microtubules. Nat. Struct. Mol. Biol. 22, 345–347 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gillies, J. P., Little, S. R., Siva, A., Hancock, W. O. & DeSantis, M. E. Cargo adaptor identity controls the mechanism and kinetics of dynein activation. J. Biol. Chem. 301, 108358 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rao, Q. H. et al. Structures of outer-arm dynein array on microtubule doublet reveal a motor coordination mechanism. Nat. Struct. Mol. Biol. 28, 799–810 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Abramson, J. et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 630, 493–500 (2024).

  • D’Amico, E. A. et al. Conformational transitions of the Spindly adaptor underlie its interaction with dynein and dynactin. J. Cell Biol. https://doi.org/10.1083/jcb.202206131 (2022).

  • Huynh, W. & Vale, R. D. Disease-associated mutations in human BICD2 hyperactivate motility of dynein-dynactin. J. Cell Biol. 216, 3051–3060 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, J., Zhao, Y., Chai, P., Yildiz, A. & Zhang, K. Nde1 promotes Lis1 binding to full-length autoinhibited human dynein 1. Nat. Chem. Biol. https://doi.org/10.1038/s41589-025-01981-6 (2025).

  • Marzo, M. G., Griswold, J. M. & Markus, S. M. Pac1/LIS1 stabilizes an uninhibited conformation of dynein to coordinate its localization and activity. Nat. Cell Biol. 22, 559–569 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Markus, S. M., Marzo, M. G. & McKenney, R. J. New insights into the mechanism of dynein motor regulation by lissencephaly-1. eLife https://doi.org/10.7554/eLife.59737 (2020).

  • Elshenawy, M. M. et al. Lis1 activates dynein motility by modulating its pairing with dynactin. Nat. Cell Biol. 22, 570–578 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Htet, Z. M. et al. LIS1 promotes the formation of activated cytoplasmic dynein-1 complexes. Nat. Cell Biol. 22, 518–525 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kumari, A., Kumar, C., Wasnik, N. & Mylavarapu, S. V. S. Dynein light intermediate chains as pivotal determinants of dynein multifunctionality. J. Cell Sci. https://doi.org/10.1242/jcs.254870 (2021).

  • Lee, I. G., Cason, S. E., Alqassim, S. S., Holzbaur, E. L. F. & Dominguez, R. A tunable LIC1-adaptor interaction modulates dynein activity in a cargo-specific manner. Nat. Commun. https://doi.org/10.1038/s41467-020-19538-7 (2020).

  • Celestino, R. et al. A transient helix in the disordered region of dynein light intermediate chain links the motor to structurally diverse adaptors for cargo transport. PLoS Biol. https://doi.org/10.1371/journal.pbio.3000100 (2019).

  • Gladkova, C. et al. A molecular switch for stress-induced activation of retrograde mitochondrial transport. Preprint at bioRxiv https://doi.org/10.1101/2024.09.13.612963 (2024).

  • Tirumala, N. A. et al. Single-molecule imaging of stochastic interactions that drive dynein activation and cargo movement in cells. J. Cell Biol. https://doi.org/10.1083/jcb.202210026 (2024).

  • Fellows, A. D., Bruntraeger, M., Burgold, T., Bassett, A. R. & Carter, A. P. Dynein and dynactin move long-range but are delivered separately to the axon tip. J. Cell Biol. https://doi.org/10.1083/jcb.202309084 (2024).

  • Geohring, I. C. et al. A nucleotide code governs Lis1’s ability to relieve dynein autoinhibition. Nat. Chem. Biol. https://doi.org/10.1038/s41589-025-02096-8 (2026).

  • Ton, W. D. et al. Microtubule-binding-induced allostery triggers LIS1 dissociation from dynein prior to cargo transport. Nat. Struct. Mol. Biol. 30, 1365–1379 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Okada, K. et al. Conserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dynein. Nat. Commun. https://doi.org/10.1038/s41467-023-41466-5 (2023).

  • Qiu, R., Zhang, J. & Xiang, X. LIS1 regulates cargo-adapter-mediated activation of dynein by overcoming its autoinhibition in vivo. J. Cell Biol. 218, 3630–3646 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rao, L. et al. The power of three: dynactin associates with three dyneins under load for greater force production. Preprint at bioRxiv https://doi.org/10.1101/2025.01.14.632506 (2025).

  • McKenney, R. J., Vershinin, M., Kunwar, A., Vallee, R. B. & Gross, S. P. LIS1 and NudE induce a persistent dynein force-producing state. Cell 141, 304–314 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Baumbach, J. et al. Lissencephaly-1 is a context-dependent regulator of the human dynein complex. eLife https://doi.org/10.7554/eLife.21768 (2017).

  • Gutierrez, P. A., Ackermann, B. E., Vershinin, M. & McKenney, R. J. Differential effects of the dynein-regulatory factor Lissencephaly-1 on processive dynein-dynactin motility. J. Biol. Chem. 292, 12245–12255 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ide, A. H., DeLuca, K. F., Wiggan, O., Markus, S. M. & DeLuca, J. G. The role of kinetochore dynein in checkpoint silencing is restricted to disassembly of the corona. Mol. Biol. Cell https://doi.org/10.1091/mbc.E23-04-0130 (2023).

  • Seksek, O., Biwersi, J. & Verkman, A. S. Translational diffusion of macromolecule-sized solutes in cytoplasm and nucleus. J. Cell Biol. 138, 131–142 (1997).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ross, J. L., Wallace, K., Shuman, H., Goldman, Y. E. & Holzbaur, E. L. Processive bidirectional motion of dynein-dynactin complexes in vitro. Nat. Cell Biol. 8, 562–570 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ananthanarayanan, V. et al. Dynein motion switches from diffusive to directed upon cortical anchoring. Cell 153, 1526–1536 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Abdel-Salam, G. M. H., Girgis, M., Eid, M. M., Sayed, I. S. M. & Abdel-Hamid, M. S. A homozygous loss-of-function variant in BICD2 is associated with lissencephaly and cerebellar hypoplasia. J. Hum. Genet. 67, 669–673 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schroeder, C. M. & Vale, R. D. Assembly and activation of dynein-dynactin by the cargo adaptor protein Hook3. J. Cell Biol. 214, 309–318 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bingham, J. B., King, S. J. & Schroer, T. A. Purification of dynactin and dynein from brain tissue. Methods Enzymol. 298, 171–184 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fagiewicz, R. et al. In vitro characterization of the full-length human dynein-1 cargo adaptor BicD2. Structure 30, 1470–1478 (2022).

    Article 

    Google Scholar
     

  • Bonet-Ponce, L. et al. LRRK2 mediates tubulation and vesicle sorting from lysosomes. Sci. Adv. https://doi.org/10.1126/sciadv.abb2454 (2020).

  • Wozniak, A. L., Long, A., Jones-Jamtgaard, K. N. & Weinman, S. A. Hepatitis C virus promotes virion secretion through cleavage of the Rab7 adaptor protein RILP. Proc. Natl Acad. Sci. USA 113, 12484–12489 (2016).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Birsa, N. et al. Lysine 27 ubiquitination of the mitochondrial transport protein Miro is dependent on serine 65 of the Parkin ubiquitin ligase. J. Biol. Chem. 289, 14569–14582 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mastronarde, D. N. Automated electron microscope tomography using robust prediction of specimen movements. J. Struct. Biol. 152, 36–51 (2005).

    Article 
    PubMed 

    Google Scholar
     

  • Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, K. Gctf: Real-time CTF determination and correction. J. Struct. Biol. 193, 1–12 (2016).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Chai, P., Rao, Q., Wang, Y. & Zhang, K. High-resolution structural analysis of dyneins by cryo-electron microscopy. Methods Mol. Biol. 2623, 257–279 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chai, P., Rao, Q. & Zhang, K. Multi-curve fitting and tubulin-lattice signal removal for structure determination of large microtubule-based motors. J. Struct. Biol. 214, 107897 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Goddard, T. D. et al. UCSF ChimeraX: meeting modern challenges in visualization and analysis. Protein Sci. 27, 14–25 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lau, C. K. et al. Cryo-EM reveals the complex architecture of dynactin’s shoulder region and pointed end. EMBO J. 40, e106164 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kidmose, R. T. et al. Namdinator – automatic molecular dynamics flexible fitting of structural models into cryo-EM and crystallography experimental maps. IUCrJ 6, 526–531 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Casanal, A., Lohkamp, B. & Emsley, P. Current developments in Coot for macromolecular model building of electron cryo-microscopy and crystallographic data. Protein Sci. 29, 1069–1078 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D 66, 12–21 (2010).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Afonine, P. V. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallogr. D 74, 531–544 (2018).

    Article 
    ADS 
    CAS 

    Google Scholar
     

  • RELATED ARTICLES

    Most Popular

    Recent Comments