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

Molecular Biology of the Cell
Julie K Monda, Iain M Cheeseman

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.

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Citations

Oct 8, 2020·Médecine sciences : M/S·Sara CabetDamien Sanlaville
Jan 5, 2021·Frontiers in Neuroscience·Jaseph Soto-PerezRahul N Kanadia

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Methods Mentioned

BETA
affinity purifications
immunoprecipitation
immunoprecipitations
dissection
PCR
flow cytometry

Software Mentioned

Adobe Photoshop
DeltaVision
Image Studio Lite
Metamorph
SEQUEST

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