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Elife. 2019 Jul 26;8. pii: e49677. doi: 10.7554/eLife.49677.

Ataxin-7 and Non-stop coordinate SCAR protein levels, subcellular localization, and actin cytoskeleton organization.

Author information

University of Missouri - Kansas City, Kansas City, United States.
Stowers Institute for Medical Research, Kansas City, United States.
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, United States.


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.


Ataxin7; D. melanogaster; Non-stop; SAGA complex; WAVE regulatory complex; actin; cell biology; neurobiology; neuroscience

Conflict of interest statement

VC, AT, PM, TM, SM, DH, PG, EM, JJ, EL, SR, LS, RP, SM, LF, MW, RM No competing interests declared

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