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Citation
Cloud, V., Thapa, A., Morales-Sosa, P., Miller, T.M., Miller, S.A., Holsapple, D., Gerhart, P.M., Momtahan, E., Jack, J.L., Leiva, E., Rapp, S.R., Shelton, L.G., Pierce, R.A., Martin-Brown, S., Florens, L., Washburn, M.P., Mohan, R.D. (2019). Ataxin-7 and Non-stop coordinate SCAR protein levels, subcellular localization, and actin cytoskeleton organization.  eLife 8(): e49677.
FlyBase ID
FBrf0243242
Publication Type
Research paper
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 SCAR did not significantly rescue knockdown of Atxn7, but heterozygous mutation of Atxn7 rescued haploinsufficiency of SCAR.

PubMed ID
PubMed Central ID
PMC6693919 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    eLife
    Title
    eLife
    ISBN/ISSN
    2050-084X
    Data From Reference
    Alleles (8)
    Genes (6)
    Human Disease Models (1)
    Physical Interactions (6)
    Cell Lines (2)
    Insertions (1)
    Transgenic Constructs (4)