Conserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dynein
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Abstract
Processive transport by the microtubule motor cytoplasmic dynein requires the regulated assembly of a dynein-dynactin-adapter complex. Interactions between dynein and dynactin were initially ascribed to the dynein intermediate chain N-terminus and the dynactin subunit p150 Glued . However, recent cryo-EM structures have not resolved this interaction, questioning its importance. The intermediate chain also interacts with Nde1/Ndel1, which compete with p150 Glued for binding. We reveal that the intermediate chain N-terminus is a critical evolutionarily conserved hub that interacts with dynactin and Ndel1, the latter of which recruits LIS1 to drive complex assembly. In additon to revealing that the intermediate chain N-terminus is likely bound to p150 Glued in active transport complexes, our data support a model whereby Ndel1-LIS1 must dissociate prior to LIS1 being handed off to dynein in temporally discrete steps. Our work reveals previously unknown steps in the dynein activation pathway, and provide insight into the integrated activities of LIS1/Ndel1 and dynactin/cargo-adapters.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Opposing motor activities are required for the organization of the mammalian mitotic spindle pole.
Gaglio, T., Saredi, A., Bingham, J. B., Hasbani, M. J., Gill, S. R., Schroer, T. A., & Compton, D. A. (1996) · The Journal of cell biology · doi:10.1083/jcb.135.2.399 · Cited by 290 · see citing works
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- Authors
- Okada, K., Iyer, B. R., Lammers, L. G., Gutierrez, P. A., Li, W., Markus, S. M., & McKenney, R. J.
- Affiliations
- University of California, Davis (US)
- Colorado State University (US)
- Columbia University (US)
- Corresponding author
- Markus, Steven M.
- McKenney, Richard J.
- Venue
- Nature Communications
- Published
- 2023-09-20
- Volume
- 14
- Issue
- 1
- Pages
- 5833-5833
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10511499
- OpenAlex
- W4386889890
- Cited by
- 24
- References
- 2
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 7 · 2023: 3 · 2022: 1
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (2R35GM124889, R35GM139483)
- U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (4R00NS089428)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- cytoplasmic dynein, dynein intermediate chain, Ndel1, NDE1, dynactin, LIS1, dynein activation, microtubule motor proteins
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