Nde1 promotes diverse dynein functions through differential interactions and exhibits an isoform-specific proteasome association
Name
mbc.e18-07-0418.pdf
Description
Published version
Size
5.48 MB
Format
Adobe PDF
Checksum (MD5)
161d9eed3b574866f20060923374645b
Author(s)
Monda, Julie Kathryn
Cheeseman, Iain M
Date Issued
September 2018
Journal
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Citation
Monda, Julie K. and Iain M. Cheeseman. "Nde1 promotes diverse dynein functions through differential interactions and exhibits an isoform-specific proteasome association." Molecular Biology of the Cell 29, 19 (September 2018): 2243-2357 © 2018 The Authors
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Creative Commons Attribution Noncommercial 3.0 unported license
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DOI of Published Version
https://doi.org/10.1091/mbc.e18-07-0418
