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Nde1 promotes diverse dynein functions through differential interactions and exhibits an isoform-specific proteasome association

Nde1 is a key regulator of cytoplasmic dynein, binding directly to both dynein itself and the dynein adaptor, Lis1. Nde1 and Lis1 are thought to function together to promote dynein function, yet mutations in each result in distinct neurodevelopment phenotypes. To reconcile these phenotypic differenc...

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Detalles Bibliográficos
Autores principales: Monda, Julie K., Cheeseman, Iain M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249811/
https://www.ncbi.nlm.nih.gov/pubmed/30024347
http://dx.doi.org/10.1091/mbc.E18-07-0418
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author Monda, Julie K.
Cheeseman, Iain M.
author_facet Monda, Julie K.
Cheeseman, Iain M.
author_sort Monda, Julie K.
collection PubMed
description Nde1 is a key regulator of cytoplasmic dynein, binding directly to both dynein itself and the dynein adaptor, Lis1. Nde1 and Lis1 are thought to function together to promote dynein function, yet mutations in each result in distinct neurodevelopment phenotypes. To reconcile these phenotypic differences, we sought to dissect the contribution of Nde1 to dynein regulation and explore the cellular functions of Nde1. Here we show that an Nde1–Lis1 interaction is required for spindle pole focusing and Golgi organization but is largely dispensable for centrosome placement, despite Lis1 itself being required. Thus, diverse functions of dynein rely on distinct Nde1- and Lis1-mediated regulatory mechanisms. Additionally, we discovered a robust, isoform-specific interaction between human Nde1 and the 26S proteasome and identify precise mutations in Nde1 that disrupt the proteasome interaction. Together, our work suggests that Nde1 makes unique contributions to human neurodevelopment through its regulation of both dynein and proteasome function.
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spelling pubmed-62498112018-11-30 Nde1 promotes diverse dynein functions through differential interactions and exhibits an isoform-specific proteasome association Monda, Julie K. Cheeseman, Iain M. Mol Biol Cell Articles Nde1 is a key regulator of cytoplasmic dynein, binding directly to both dynein itself and the dynein adaptor, Lis1. Nde1 and Lis1 are thought to function together to promote dynein function, yet mutations in each result in distinct neurodevelopment phenotypes. To reconcile these phenotypic differences, we sought to dissect the contribution of Nde1 to dynein regulation and explore the cellular functions of Nde1. Here we show that an Nde1–Lis1 interaction is required for spindle pole focusing and Golgi organization but is largely dispensable for centrosome placement, despite Lis1 itself being required. Thus, diverse functions of dynein rely on distinct Nde1- and Lis1-mediated regulatory mechanisms. Additionally, we discovered a robust, isoform-specific interaction between human Nde1 and the 26S proteasome and identify precise mutations in Nde1 that disrupt the proteasome interaction. Together, our work suggests that Nde1 makes unique contributions to human neurodevelopment through its regulation of both dynein and proteasome function. The American Society for Cell Biology 2018-09-15 /pmc/articles/PMC6249811/ /pubmed/30024347 http://dx.doi.org/10.1091/mbc.E18-07-0418 Text en © 2018 Monda and Cheeseman. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Monda, Julie K.
Cheeseman, Iain M.
Nde1 promotes diverse dynein functions through differential interactions and exhibits an isoform-specific proteasome association
title Nde1 promotes diverse dynein functions through differential interactions and exhibits an isoform-specific proteasome association
title_full Nde1 promotes diverse dynein functions through differential interactions and exhibits an isoform-specific proteasome association
title_fullStr Nde1 promotes diverse dynein functions through differential interactions and exhibits an isoform-specific proteasome association
title_full_unstemmed Nde1 promotes diverse dynein functions through differential interactions and exhibits an isoform-specific proteasome association
title_short Nde1 promotes diverse dynein functions through differential interactions and exhibits an isoform-specific proteasome association
title_sort nde1 promotes diverse dynein functions through differential interactions and exhibits an isoform-specific proteasome association
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249811/
https://www.ncbi.nlm.nih.gov/pubmed/30024347
http://dx.doi.org/10.1091/mbc.E18-07-0418
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