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Nde1 promotes Lis1-mediated activation of dynein

Cytoplasmic dynein drives the motility and force generation functions towards the microtubule minus end. The assembly of dynein with dynactin and a cargo adaptor in an active transport complex is facilitated by Lis1 and Nde1/Ndel1. Recent studies proposed that Lis1 relieves dynein from its autoinhib...

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Detalles Bibliográficos
Autores principales: Zhao, Yuanchang, Oten, Sena, Yildiz, Ahmet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10632352/
https://www.ncbi.nlm.nih.gov/pubmed/37940657
http://dx.doi.org/10.1038/s41467-023-42907-x
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author Zhao, Yuanchang
Oten, Sena
Yildiz, Ahmet
author_facet Zhao, Yuanchang
Oten, Sena
Yildiz, Ahmet
author_sort Zhao, Yuanchang
collection PubMed
description Cytoplasmic dynein drives the motility and force generation functions towards the microtubule minus end. The assembly of dynein with dynactin and a cargo adaptor in an active transport complex is facilitated by Lis1 and Nde1/Ndel1. Recent studies proposed that Lis1 relieves dynein from its autoinhibited conformation, but the physiological function of Nde1/Ndel1 remains elusive. Here, we investigate how human Nde1 and Lis1 regulate the assembly and subsequent motility of mammalian dynein using in vitro reconstitution and single molecule imaging. We find that Nde1 recruits Lis1 to autoinhibited dynein and promotes Lis1-mediated assembly of dynein-dynactin adaptor complexes. Nde1 can compete with the α2 subunit of platelet activator factor acetylhydrolase 1B (PAF-AH1B) for the binding of Lis1, which suggests that Nde1 may disrupt PAF-AH1B recruitment of Lis1 as a noncatalytic subunit, thus promoting Lis1 binding to dynein. Before the initiation of motility, the association of dynactin with dynein triggers the dissociation of Nde1 from dynein by competing against Nde1 binding to the dynein intermediate chain. Our results provide a mechanistic explanation for how Nde1 and Lis1 synergistically activate the dynein transport machinery.
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spelling pubmed-106323522023-11-10 Nde1 promotes Lis1-mediated activation of dynein Zhao, Yuanchang Oten, Sena Yildiz, Ahmet Nat Commun Article Cytoplasmic dynein drives the motility and force generation functions towards the microtubule minus end. The assembly of dynein with dynactin and a cargo adaptor in an active transport complex is facilitated by Lis1 and Nde1/Ndel1. Recent studies proposed that Lis1 relieves dynein from its autoinhibited conformation, but the physiological function of Nde1/Ndel1 remains elusive. Here, we investigate how human Nde1 and Lis1 regulate the assembly and subsequent motility of mammalian dynein using in vitro reconstitution and single molecule imaging. We find that Nde1 recruits Lis1 to autoinhibited dynein and promotes Lis1-mediated assembly of dynein-dynactin adaptor complexes. Nde1 can compete with the α2 subunit of platelet activator factor acetylhydrolase 1B (PAF-AH1B) for the binding of Lis1, which suggests that Nde1 may disrupt PAF-AH1B recruitment of Lis1 as a noncatalytic subunit, thus promoting Lis1 binding to dynein. Before the initiation of motility, the association of dynactin with dynein triggers the dissociation of Nde1 from dynein by competing against Nde1 binding to the dynein intermediate chain. Our results provide a mechanistic explanation for how Nde1 and Lis1 synergistically activate the dynein transport machinery. Nature Publishing Group UK 2023-11-09 /pmc/articles/PMC10632352/ /pubmed/37940657 http://dx.doi.org/10.1038/s41467-023-42907-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhao, Yuanchang
Oten, Sena
Yildiz, Ahmet
Nde1 promotes Lis1-mediated activation of dynein
title Nde1 promotes Lis1-mediated activation of dynein
title_full Nde1 promotes Lis1-mediated activation of dynein
title_fullStr Nde1 promotes Lis1-mediated activation of dynein
title_full_unstemmed Nde1 promotes Lis1-mediated activation of dynein
title_short Nde1 promotes Lis1-mediated activation of dynein
title_sort nde1 promotes lis1-mediated activation of dynein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10632352/
https://www.ncbi.nlm.nih.gov/pubmed/37940657
http://dx.doi.org/10.1038/s41467-023-42907-x
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