Ataxin-7 and Non-stop coordinate SCAR protein levels, subcellular localization, and actin cytoskeleton organization
- University of Missouri - Kansas City, United States
- Stowers Institute for Medical Research, United States
Abstract
Atxn7, a subunit of SAGA chromatin remodeling complex, is subject to polyglutamine expansion at the amino terminus, causing spinocerebellar ataxia type 7 (SCA7), a progressive retinal and neurodegenerative disease. Within SAGA, the Atxn7 amino terminus anchors Non-stop, a deubiquitinase, to the complex. To understand the scope of Atxn7-dependent regulation of Non-stop, substrates of the deubiquitinase were sought. This revealed Non-stop, dissociated from Atxn7, interacts with Arp2/3 and WAVE regulatory complexes (WRC), which control actin cytoskeleton assembly. There, Non-stop countered polyubiquitination and proteasomal degradation of WRC subunit SCAR. Dependent on conserved WRC interacting receptor sequences (WIRS), Non-stop augmentation increased protein levels, and directed subcellular localization, of SCAR, decreasing cell area and number of protrusions. In vivo, heterozygous mutation of Atxn7 rescued haploinsufficiency of SCAR, but heterozygous mutation of SCAR did not significantly rescue knockdown of Atxn7.
Data availability
All proteomics data are available in the MassIVE repository. The permanent URL to the dataset is: ftp://massive.ucsd.edu/MSV000082625. The data is also accessible from: ProteomeXChange accession: PXD010462 http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD010462. MassIVE | Accession ID: MSV000082625 - ProteomeXchange | Accession ID: PXD010462
Article and author information
Author details
Michael P Washburn
Funding
National Institutes of Health (NIGMS grant 5R35GM118068)
- Ryan D Mohan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Irwin Davidson, Institut de Génétique et de Biologie Moléculaire et Cellulaire, France
Version history
- Received: June 25, 2019
- Accepted: July 22, 2019
- Accepted Manuscript published: July 26, 2019 (version 1)
- Version of Record published: August 14, 2019 (version 2)
Copyright
© 2019, Cloud 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.
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Ataxin-7 and Non-stop coordinate SCAR protein levels, subcellular localization, and actin cytoskeleton organization
eLife 8:e49677.
https://doi.org/10.7554/eLife.49677
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