UMMS Affiliation

Department of Neurology

Date

12-9-2015

Document Type

Article

Disciplines

Cell Biology | Molecular and Cellular Neuroscience | Nervous System Diseases | Neurology

Abstract

Microsatellite expansions are the leading cause of numerous neurodegenerative disorders. Here we demonstrate that GGGGCC and CAG microsatellite repeat RNAs associated with C9orf72 in ALS/FTD and with polyglutamine diseases, respectively, localize to neuritic granules that undergo active transport into distal neuritic segments. In cultured mammalian spinal cord neurons, the presence of neuritic GGGGCC repeat RNA correlates with neuronal branching defects and the repeat RNA localizes to granules that label with FMRP, a transport granule component. Using a Drosophila GGGGCC expansion disease model, we characterize dendritic branching defects that are modulated by FMRP and Orb2. The human orthologues of these modifiers are misregulated in induced pluripotent stem cell-differentiated neurons from GGGGCC expansion carriers. These data suggest that expanded repeat RNAs interact with the mRNA transport and translation machinery, causing transport granule dysfunction. This could be a novel mechanism contributing to the neuronal defects associated with C9orf72 and other microsatellite expansion diseases.

Rights and Permissions

Citation: Elife. 2015 Dec 9;4. pii: e08881. doi: 10.7554/eLife.08881. Link to article on publisher's site

DOI of Published Version

10.7554/eLife.08881

Comments

© 2015, Schweizer Burguete et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Related Resources

Link to Article in PubMed

Keywords

D. melanogaster, cell biology

Journal Title

eLife

PubMed ID

26650351

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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