Ataxin-7 and Non-stop coordinate SCAR protein levels, subcellular localization, and actin cytoskeleton organization
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 comp...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/49677 |
| _version_ | 1828380189247143936 |
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| author | Veronica Cloud Ada Thapa Pedro Morales-Sosa Tayla M Miller Sara A Miller Daniel Holsapple Paige M Gerhart Elaheh Momtahan Jarrid L Jack Edgardo Leiva Sarah R Rapp Lauren G Shelton Richard A Pierce Skylar Martin-Brown Laurence Florens Michael P Washburn Ryan D Mohan |
| author_facet | Veronica Cloud Ada Thapa Pedro Morales-Sosa Tayla M Miller Sara A Miller Daniel Holsapple Paige M Gerhart Elaheh Momtahan Jarrid L Jack Edgardo Leiva Sarah R Rapp Lauren G Shelton Richard A Pierce Skylar Martin-Brown Laurence Florens Michael P Washburn Ryan D Mohan |
| author_sort | Veronica Cloud |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T03:52:26Z |
| format | Article |
| id | doaj.art-6e9fff0a29524fd48b00d077b354eed6 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T03:52:26Z |
| publishDate | 2019-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6e9fff0a29524fd48b00d077b354eed62022-12-22T02:03:12ZengeLife Sciences Publications LtdeLife2050-084X2019-07-01810.7554/eLife.49677Ataxin-7 and Non-stop coordinate SCAR protein levels, subcellular localization, and actin cytoskeleton organizationVeronica Cloud0https://orcid.org/0000-0003-3701-4150Ada Thapa1Pedro Morales-Sosa2Tayla M Miller3Sara A Miller4Daniel Holsapple5Paige M Gerhart6Elaheh Momtahan7Jarrid L Jack8Edgardo Leiva9Sarah R Rapp10Lauren G Shelton11Richard A Pierce12Skylar Martin-Brown13Laurence Florens14Michael P Washburn15https://orcid.org/0000-0001-7568-2585Ryan D Mohan16https://orcid.org/0000-0002-7624-4605University of Missouri - Kansas City, Kansas City, United StatesUniversity of Missouri - Kansas City, Kansas City, United StatesUniversity of Missouri - Kansas City, Kansas City, United StatesUniversity of Missouri - Kansas City, Kansas City, United StatesUniversity of Missouri - Kansas City, Kansas City, United StatesUniversity of Missouri - Kansas City, Kansas City, United StatesUniversity of Missouri - Kansas City, Kansas City, United StatesUniversity of Missouri - Kansas City, Kansas City, United StatesUniversity of Missouri - Kansas City, Kansas City, United StatesUniversity of Missouri - Kansas City, Kansas City, United StatesUniversity of Missouri - Kansas City, Kansas City, United StatesStowers Institute for Medical Research, Kansas City, United StatesStowers Institute for Medical Research, Kansas City, United StatesStowers Institute for Medical Research, Kansas City, United StatesStowers Institute for Medical Research, Kansas City, United StatesStowers Institute for Medical Research, Kansas City, United States; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, United StatesUniversity of Missouri - Kansas City, Kansas City, United StatesAtxn7, 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.https://elifesciences.org/articles/49677Ataxin7neurobiologyactinWAVE regulatory complexSAGA complexNon-stop |
| spellingShingle | Veronica Cloud Ada Thapa Pedro Morales-Sosa Tayla M Miller Sara A Miller Daniel Holsapple Paige M Gerhart Elaheh Momtahan Jarrid L Jack Edgardo Leiva Sarah R Rapp Lauren G Shelton Richard A Pierce Skylar Martin-Brown Laurence Florens Michael P Washburn Ryan D Mohan Ataxin-7 and Non-stop coordinate SCAR protein levels, subcellular localization, and actin cytoskeleton organization eLife Ataxin7 neurobiology actin WAVE regulatory complex SAGA complex Non-stop |
| title | Ataxin-7 and Non-stop coordinate SCAR protein levels, subcellular localization, and actin cytoskeleton organization |
| title_full | Ataxin-7 and Non-stop coordinate SCAR protein levels, subcellular localization, and actin cytoskeleton organization |
| title_fullStr | Ataxin-7 and Non-stop coordinate SCAR protein levels, subcellular localization, and actin cytoskeleton organization |
| title_full_unstemmed | Ataxin-7 and Non-stop coordinate SCAR protein levels, subcellular localization, and actin cytoskeleton organization |
| title_short | Ataxin-7 and Non-stop coordinate SCAR protein levels, subcellular localization, and actin cytoskeleton organization |
| title_sort | ataxin 7 and non stop coordinate scar protein levels subcellular localization and actin cytoskeleton organization |
| topic | Ataxin7 neurobiology actin WAVE regulatory complex SAGA complex Non-stop |
| url | https://elifesciences.org/articles/49677 |
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