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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...

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Autores principales: Baile, Matthew G., Guiney, Evan L., Sanford, Ethan J., MacGurn, Jason A., Smolka, Marcus B., Emr, Scott D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
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.
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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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