Title

A Mouse Neurodegenerative Dynein Heavy Chain Mutation Alters Dynein Motility And Localization In Neurospora Crassa

Keywords

Cytoplasmic dynein; Dynactin; Intracellular transport; Legs at odd angles (Loa) mutation; Microtubules; Neurospora crassa

Abstract

Cytoplasmic dynein is responsible for the transport and delivery of cargoes in organisms ranging from humans to fungi. Dysfunction of dynein motor machinery due to mutations in dynein or its activating complex dynactin can result in one of several neurological diseases in mammals. The mouse Legs at odd angles (Loa) mutation in the tail domain of the dynein heavy chain has been shown to lead to progressive neurodegeneration in mice. The mechanism by which the Loa mutation affects dynein function is just beginning to be understood. In this work, we generated the dynein tail mutation observed in Loa mice into the Neurospora crassa genome and utilized cell biological and complementing biochemical approaches to characterize how that tail mutation affected dynein function. We determined that the Loa mutation exhibits several subtle defects upon dynein function in N. crassa that were not seen in mice, including alterations in dynein localization, impaired velocity of vesicle transport, and in the biochemical properties of purified motors. Our work provides new information on the role of the tail domain on dynein function and points out areas of future research that will be of interest to pursue in mammalian systems. © 2012 Wiley Periodicals, Inc.

Publication Date

9-1-2012

Publication Title

Cytoskeleton

Volume

69

Issue

9

Number of Pages

613-624

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1002/cm.21049

Socpus ID

84866490577 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84866490577

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