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Cdh1-APC Regulates Protein Synthesis and Stress Granules in Neurons through an FMRP-Dependent Mechanism
Maintaining a balance between protein degradation and protein synthesis is necessary for neurodevelopment. Although the E3 ubiquitin ligase anaphase promoting complex and its regulatory subunit Cdh1 (Cdh1-APC) has been shown to regulate learning and memory, the underlying mechanisms are unclear. Her...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236060/ https://www.ncbi.nlm.nih.gov/pubmed/32434143 http://dx.doi.org/10.1016/j.isci.2020.101132 |
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author | Valdez-Sinon, Arielle N. Lai, Austin Shi, Liang Lancaster, Carly L. Gokhale, Avanti Faundez, Victor Bassell, Gary J. |
author_facet | Valdez-Sinon, Arielle N. Lai, Austin Shi, Liang Lancaster, Carly L. Gokhale, Avanti Faundez, Victor Bassell, Gary J. |
author_sort | Valdez-Sinon, Arielle N. |
collection | PubMed |
description | Maintaining a balance between protein degradation and protein synthesis is necessary for neurodevelopment. Although the E3 ubiquitin ligase anaphase promoting complex and its regulatory subunit Cdh1 (Cdh1-APC) has been shown to regulate learning and memory, the underlying mechanisms are unclear. Here, we have identified a role of Cdh1-APC as a regulator of protein synthesis in neurons. Proteomic profiling revealed that Cdh1-APC interacts with known regulators of translation, including stress granule proteins. Inhibition of Cdh1-APC activity caused an increase in stress granule formation that is dependent on fragile X mental retardation protein (FMRP). We propose a model in which Cdh1-APC targets stress granule proteins, such as FMRP, and inhibits the formation of stress granules, leading to protein synthesis. Elucidation of a role for Cdh1-APC in regulation of stress granules and protein synthesis in neurons has implications for how Cdh1-APC can regulate protein-synthesis-dependent synaptic plasticity underlying learning and memory. |
format | Online Article Text |
id | pubmed-7236060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-72360602020-05-22 Cdh1-APC Regulates Protein Synthesis and Stress Granules in Neurons through an FMRP-Dependent Mechanism Valdez-Sinon, Arielle N. Lai, Austin Shi, Liang Lancaster, Carly L. Gokhale, Avanti Faundez, Victor Bassell, Gary J. iScience Article Maintaining a balance between protein degradation and protein synthesis is necessary for neurodevelopment. Although the E3 ubiquitin ligase anaphase promoting complex and its regulatory subunit Cdh1 (Cdh1-APC) has been shown to regulate learning and memory, the underlying mechanisms are unclear. Here, we have identified a role of Cdh1-APC as a regulator of protein synthesis in neurons. Proteomic profiling revealed that Cdh1-APC interacts with known regulators of translation, including stress granule proteins. Inhibition of Cdh1-APC activity caused an increase in stress granule formation that is dependent on fragile X mental retardation protein (FMRP). We propose a model in which Cdh1-APC targets stress granule proteins, such as FMRP, and inhibits the formation of stress granules, leading to protein synthesis. Elucidation of a role for Cdh1-APC in regulation of stress granules and protein synthesis in neurons has implications for how Cdh1-APC can regulate protein-synthesis-dependent synaptic plasticity underlying learning and memory. Elsevier 2020-05-01 /pmc/articles/PMC7236060/ /pubmed/32434143 http://dx.doi.org/10.1016/j.isci.2020.101132 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Valdez-Sinon, Arielle N. Lai, Austin Shi, Liang Lancaster, Carly L. Gokhale, Avanti Faundez, Victor Bassell, Gary J. Cdh1-APC Regulates Protein Synthesis and Stress Granules in Neurons through an FMRP-Dependent Mechanism |
title | Cdh1-APC Regulates Protein Synthesis and Stress Granules in Neurons through an FMRP-Dependent Mechanism |
title_full | Cdh1-APC Regulates Protein Synthesis and Stress Granules in Neurons through an FMRP-Dependent Mechanism |
title_fullStr | Cdh1-APC Regulates Protein Synthesis and Stress Granules in Neurons through an FMRP-Dependent Mechanism |
title_full_unstemmed | Cdh1-APC Regulates Protein Synthesis and Stress Granules in Neurons through an FMRP-Dependent Mechanism |
title_short | Cdh1-APC Regulates Protein Synthesis and Stress Granules in Neurons through an FMRP-Dependent Mechanism |
title_sort | cdh1-apc regulates protein synthesis and stress granules in neurons through an fmrp-dependent mechanism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236060/ https://www.ncbi.nlm.nih.gov/pubmed/32434143 http://dx.doi.org/10.1016/j.isci.2020.101132 |
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