Conserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dynein
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 p150Glued. However, re...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41466-5 |
| _version_ | 1797558244265164800 |
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| author | Kyoko Okada Bharat R. Iyer Lindsay G. Lammers Pedro A. Gutierrez Wenzhe Li Steven M. Markus Richard J. McKenney |
| author_facet | Kyoko Okada Bharat R. Iyer Lindsay G. Lammers Pedro A. Gutierrez Wenzhe Li Steven M. Markus Richard J. McKenney |
| author_sort | Kyoko Okada |
| collection | DOAJ |
| description | 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 p150Glued. However, recent cryo-EM structures have not resolved this interaction, questioning its importance. The intermediate chain also interacts with Nde1/Ndel1, which compete with p150Glued 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 p150Glued 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. |
| first_indexed | 2024-03-10T17:28:36Z |
| format | Article |
| id | doaj.art-986beca8951b42fa9ebd4f5a2cf41ad4 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:28:36Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-986beca8951b42fa9ebd4f5a2cf41ad42023-11-20T10:06:45ZengNature PortfolioNature Communications2041-17232023-09-0114111910.1038/s41467-023-41466-5Conserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dyneinKyoko Okada0Bharat R. Iyer1Lindsay G. Lammers2Pedro A. Gutierrez3Wenzhe Li4Steven M. Markus5Richard J. McKenney6Department of Molecular and Cellular Biology, University of California, DavisDepartment of Biochemistry and Molecular Biology, Colorado State UniversityDepartment of Biochemistry and Molecular Biology, Colorado State UniversityDepartment of Molecular and Cellular Biology, University of California, DavisDepartment of Molecular and Cellular Biology, University of California, DavisDepartment of Biochemistry and Molecular Biology, Colorado State UniversityDepartment of Molecular and Cellular Biology, University of California, DavisAbstract 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 p150Glued. However, recent cryo-EM structures have not resolved this interaction, questioning its importance. The intermediate chain also interacts with Nde1/Ndel1, which compete with p150Glued 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 p150Glued 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.https://doi.org/10.1038/s41467-023-41466-5 |
| spellingShingle | Kyoko Okada Bharat R. Iyer Lindsay G. Lammers Pedro A. Gutierrez Wenzhe Li Steven M. Markus Richard J. McKenney Conserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dynein Nature Communications |
| title | Conserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dynein |
| title_full | Conserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dynein |
| title_fullStr | Conserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dynein |
| title_full_unstemmed | Conserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dynein |
| title_short | Conserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dynein |
| title_sort | conserved roles for the dynein intermediate chain and ndel1 in assembly and activation of dynein |
| url | https://doi.org/10.1038/s41467-023-41466-5 |
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