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Activity of a ubiquitin ligase adaptor is regulated by disordered insertions in its arrestin domain
The protein composition of the plasma membrane is rapidly remodeled in response to changes in nutrient availability or cellular stress. This occurs, in part, through the selective ubiquitylation and endocytosis of plasma membrane proteins, which in the yeast Saccharomyces cerevisiae is mediated by t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880881/ https://www.ncbi.nlm.nih.gov/pubmed/31618110 http://dx.doi.org/10.1091/mbc.E19-08-0451 |
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author | Baile, Matthew G. Guiney, Evan L. Sanford, Ethan J. MacGurn, Jason A. Smolka, Marcus B. Emr, Scott D. |
author_facet | Baile, Matthew G. Guiney, Evan L. Sanford, Ethan J. MacGurn, Jason A. Smolka, Marcus B. Emr, Scott D. |
author_sort | Baile, Matthew G. |
collection | PubMed |
description | The protein composition of the plasma membrane is rapidly remodeled in response to changes in nutrient availability or cellular stress. This occurs, in part, through the selective ubiquitylation and endocytosis of plasma membrane proteins, which in the yeast Saccharomyces cerevisiae is mediated by the HECT E3 ubiquitin ligase Rsp5 and arrestin-related trafficking (ART) adaptors. Here, we provide evidence that the ART protein family members are composed of an arrestin fold with interspersed disordered loops. Using Art1 as a model, we show that these loop and tail regions, while not strictly required for function, regulate its activity through two separate mechanisms. Disruption of one loop mediates Art1 substrate specificity. Other loops are subjected to phosphorylation in a manner dependent on the Pho85 cyclins Clg1 and Pho80. Phosphorylation of the loops controls Art1’s localization to the plasma membrane, which promotes cargo ubiquitylation and endocytosis, demonstrating a mechanism through which Art1 activity is regulated. |
format | Online Article Text |
id | pubmed-6880881 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-68808812020-02-16 Activity of a ubiquitin ligase adaptor is regulated by disordered insertions in its arrestin domain Baile, Matthew G. Guiney, Evan L. Sanford, Ethan J. MacGurn, Jason A. Smolka, Marcus B. Emr, Scott D. Mol Biol Cell Articles The protein composition of the plasma membrane is rapidly remodeled in response to changes in nutrient availability or cellular stress. This occurs, in part, through the selective ubiquitylation and endocytosis of plasma membrane proteins, which in the yeast Saccharomyces cerevisiae is mediated by the HECT E3 ubiquitin ligase Rsp5 and arrestin-related trafficking (ART) adaptors. Here, we provide evidence that the ART protein family members are composed of an arrestin fold with interspersed disordered loops. Using Art1 as a model, we show that these loop and tail regions, while not strictly required for function, regulate its activity through two separate mechanisms. Disruption of one loop mediates Art1 substrate specificity. Other loops are subjected to phosphorylation in a manner dependent on the Pho85 cyclins Clg1 and Pho80. Phosphorylation of the loops controls Art1’s localization to the plasma membrane, which promotes cargo ubiquitylation and endocytosis, demonstrating a mechanism through which Art1 activity is regulated. The American Society for Cell Biology 2019-12-01 /pmc/articles/PMC6880881/ /pubmed/31618110 http://dx.doi.org/10.1091/mbc.E19-08-0451 Text en © 2019 Baile, Guiney, et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Articles Baile, Matthew G. Guiney, Evan L. Sanford, Ethan J. MacGurn, Jason A. Smolka, Marcus B. Emr, Scott D. Activity of a ubiquitin ligase adaptor is regulated by disordered insertions in its arrestin domain |
title | Activity of a ubiquitin ligase adaptor is regulated by disordered insertions in its arrestin domain |
title_full | Activity of a ubiquitin ligase adaptor is regulated by disordered insertions in its arrestin domain |
title_fullStr | Activity of a ubiquitin ligase adaptor is regulated by disordered insertions in its arrestin domain |
title_full_unstemmed | Activity of a ubiquitin ligase adaptor is regulated by disordered insertions in its arrestin domain |
title_short | Activity of a ubiquitin ligase adaptor is regulated by disordered insertions in its arrestin domain |
title_sort | activity of a ubiquitin ligase adaptor is regulated by disordered insertions in its arrestin domain |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880881/ https://www.ncbi.nlm.nih.gov/pubmed/31618110 http://dx.doi.org/10.1091/mbc.E19-08-0451 |
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