ArticleMolecular biology of the cell2020
Dynactin p150 promotes processive motility of DDB complexes by minimizing diffusional behavior of dynein.
Article in Molecular biology of the cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- DNA tensiometer reveals catch-bond detachment kinetics of kinesin-1, -2 and -3.bioRxiv : the preprint server for biology · 2025Article
- Efficient axonal transport of endolysosomes relies on the balanced ratio of microtubule tyrosination and detyrosination.Journal of cell science · 2024Article
- Molecular mechanism of dynein-dynactin complex assembly by LIS1.Science (New York, N.Y.) · 2024Article
- Tropomyosin 1-I/C coordinates kinesin-1 and dynein motors during oskar mRNA transport.Nature structural & molecular biology · 2024Article
- Whole-Exome Sequencing Identifies DYNC2H1 Mutations as a Cause of Jeune Asphyxiating Thoracic Dystrophy Without Extra-Skeletal Organ Involvement.International medical case reports journal · 2024Article
- Axonal transport of autophagosomes is regulated by dynein activators JIP3/JIP4 and ARF/RAB GTPases.The Journal of cell biology · 2023Article
- Vesicles driven by dynein and kinesin exhibit directional reversals without regulators.Nature communications · 2023Article
- Simulations suggest robust microtubule attachment of kinesin and dynein in antagonistic pairs.Biophysical journal · 2023Article
- The meiotic LINC complex component KASH5 is an activating adaptor for cytoplasmic dynein.The Journal of cell biology · 2023Article
- Axonal transport of autophagosomes is regulated by dynein activators JIP3/JIP4 and ARF/RAB GTPases.bioRxiv : the preprint server for biology · 2023Article
- Selective motor activation in organelle transport along axons.Nature reviews. Molecular cell biology · 2022Review
- Article
- Coil-to-α-helix transition at the Nup358-BicD2 interface activates BicD2 for dynein recruitment.eLife · 2022Article
- Advances in the study of axon-associated vesicles.Frontiers in molecular neuroscience · 2022Review
- A change point analysis protocol for comparing intracellular transport by different molecular motor combinations.Mathematical biosciences and engineering : MBE · 2021Article
- Sequential dynein effectors regulate axonal autophagosome motility in a maturation-dependent pathway.The Journal of cell biology · 2021Article
- On and off controls within dynein-dynactin on native cargoes.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A septin GTPase scaffold of dynein-dynactin motors triggers retrograde lysosome transport.The Journal of cell biology · 2021Article
- Cargo-Mediated Activation of Cytoplasmic DyneinFrontiers in cell and developmental biology · 2020Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cytoplasmic dynein is activated by forming a complex with dynactin and the adaptor protein BicD2. We used interferometric scattering (iSCAT) microscopy to track dynein-dynactin-BicD2 (DDB) complexes in vitro and developed a regression-based algorithm to classify switching between processive, diffusive, and stuck motility states. We find that DDB spends 65% of its time undergoing processive stepping, 4% undergoing 1D diffusion, and the remaining time transiently stuck to the microtubule. Although the p150 subunit was previously shown to enable dynactin diffusion along microtubules, blocking p150 enhanced the proportion of time DDB diffused and reduced the time DDB processively walked. Thus, DDB diffusive behavior most likely results from dynein switching into an inactive (diffusive) state, rather than p150 tethering the complex to the microtubule. DDB-kinesin-1 complexes, formed using a DNA adapter, moved slowly and persistently, and blocking p150 led to a 70 nm/s plus-end shift in the average velocity of the complexes, in quantitative agreement with the shift of isolated DDB into the diffusive state. The data suggest a DDB activation model in which dynactin p150 enhances dynein processivity not solely by acting as a diffusive tether that maintains microtubule association, but rather by acting as an allosteric activator that promotes a conformation of dynein optimal for processive stepping. In bidirectional cargo transport driven by the opposing activities of kinesin and dynein-dynactin-BicD2, the dynactin p150 subunit promotes retrograde transport and could serve as a target for regulators of transport.
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