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TORC1 Signaling Controls the Stability and Function of α-Arrestins Aly1 and Aly2
Nutrient supply dictates cell signaling changes, which in turn regulate membrane protein trafficking. To better exploit nutrients, cells relocalize membrane transporters via selective protein trafficking. Key in this reshuffling are the α-arrestins, selective protein trafficking adaptors conserved f...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031309/ https://www.ncbi.nlm.nih.gov/pubmed/35454122 http://dx.doi.org/10.3390/biom12040533 |
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author | Bowman, Ray W. Jordahl, Eric M. Davis, Sydnie Hedayati, Stefanie Barsouk, Hannah Ozbaki-Yagan, Nejla Chiang, Annette Li, Yang O’Donnell, Allyson F. |
author_facet | Bowman, Ray W. Jordahl, Eric M. Davis, Sydnie Hedayati, Stefanie Barsouk, Hannah Ozbaki-Yagan, Nejla Chiang, Annette Li, Yang O’Donnell, Allyson F. |
author_sort | Bowman, Ray W. |
collection | PubMed |
description | Nutrient supply dictates cell signaling changes, which in turn regulate membrane protein trafficking. To better exploit nutrients, cells relocalize membrane transporters via selective protein trafficking. Key in this reshuffling are the α-arrestins, selective protein trafficking adaptors conserved from yeast to man. α-Arrestins bind membrane proteins, controlling the ubiquitination and endocytosis of many transporters. To prevent the spurious removal of membrane proteins, α-arrestin-mediated endocytosis is kept in check through phospho-inhibition. This phospho-regulation is complex, with up to 87 phospho-sites on a single α-arrestin and many kinases/phosphatases targeting α-arrestins. To better define the signaling pathways controlling paralogous α-arrestins, Aly1 and Aly2, we screened the kinase and phosphatase deletion (KinDel) library, which is an array of all non-essential kinase and phosphatase yeast deletion strains, for modifiers of Aly-mediated phenotypes. We identified many Aly regulators, but focused our studies on the TORC1 kinase, a master regulator of nutrient signaling across eukaryotes. We found that TORC1 and its signaling effectors, the Sit4 protein phosphatase and Npr1 kinase, regulate the phosphorylation and stability of Alys. When Sit4 is lost, Alys are hyperphosphorylated and destabilized in an Npr1-dependent manner. These findings add new dimensions to our understanding of TORC1 regulation of α-arrestins and have important ramifications for cellular metabolism. |
format | Online Article Text |
id | pubmed-9031309 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90313092022-04-23 TORC1 Signaling Controls the Stability and Function of α-Arrestins Aly1 and Aly2 Bowman, Ray W. Jordahl, Eric M. Davis, Sydnie Hedayati, Stefanie Barsouk, Hannah Ozbaki-Yagan, Nejla Chiang, Annette Li, Yang O’Donnell, Allyson F. Biomolecules Article Nutrient supply dictates cell signaling changes, which in turn regulate membrane protein trafficking. To better exploit nutrients, cells relocalize membrane transporters via selective protein trafficking. Key in this reshuffling are the α-arrestins, selective protein trafficking adaptors conserved from yeast to man. α-Arrestins bind membrane proteins, controlling the ubiquitination and endocytosis of many transporters. To prevent the spurious removal of membrane proteins, α-arrestin-mediated endocytosis is kept in check through phospho-inhibition. This phospho-regulation is complex, with up to 87 phospho-sites on a single α-arrestin and many kinases/phosphatases targeting α-arrestins. To better define the signaling pathways controlling paralogous α-arrestins, Aly1 and Aly2, we screened the kinase and phosphatase deletion (KinDel) library, which is an array of all non-essential kinase and phosphatase yeast deletion strains, for modifiers of Aly-mediated phenotypes. We identified many Aly regulators, but focused our studies on the TORC1 kinase, a master regulator of nutrient signaling across eukaryotes. We found that TORC1 and its signaling effectors, the Sit4 protein phosphatase and Npr1 kinase, regulate the phosphorylation and stability of Alys. When Sit4 is lost, Alys are hyperphosphorylated and destabilized in an Npr1-dependent manner. These findings add new dimensions to our understanding of TORC1 regulation of α-arrestins and have important ramifications for cellular metabolism. MDPI 2022-03-31 /pmc/articles/PMC9031309/ /pubmed/35454122 http://dx.doi.org/10.3390/biom12040533 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bowman, Ray W. Jordahl, Eric M. Davis, Sydnie Hedayati, Stefanie Barsouk, Hannah Ozbaki-Yagan, Nejla Chiang, Annette Li, Yang O’Donnell, Allyson F. TORC1 Signaling Controls the Stability and Function of α-Arrestins Aly1 and Aly2 |
title | TORC1 Signaling Controls the Stability and Function of α-Arrestins Aly1 and Aly2 |
title_full | TORC1 Signaling Controls the Stability and Function of α-Arrestins Aly1 and Aly2 |
title_fullStr | TORC1 Signaling Controls the Stability and Function of α-Arrestins Aly1 and Aly2 |
title_full_unstemmed | TORC1 Signaling Controls the Stability and Function of α-Arrestins Aly1 and Aly2 |
title_short | TORC1 Signaling Controls the Stability and Function of α-Arrestins Aly1 and Aly2 |
title_sort | torc1 signaling controls the stability and function of α-arrestins aly1 and aly2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031309/ https://www.ncbi.nlm.nih.gov/pubmed/35454122 http://dx.doi.org/10.3390/biom12040533 |
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