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Activity dependent dissociation of the Homer1 interactome

Neurons encode information by rapidly modifying synaptic protein complexes, which changes the strength of specific synaptic connections. Homer1 is abundantly expressed at glutamatergic synapses, and is known to alter its binding to metabotropic glutamate receptor 5 (mGlu5) in response to synaptic ac...

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Autores principales: Stillman, Mason, Lautz, Jonathan D., Johnson, Richard S., MacCoss, Michael J., Smith, Stephen E. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8881602/
https://www.ncbi.nlm.nih.gov/pubmed/35217690
http://dx.doi.org/10.1038/s41598-022-07179-3
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author Stillman, Mason
Lautz, Jonathan D.
Johnson, Richard S.
MacCoss, Michael J.
Smith, Stephen E. P.
author_facet Stillman, Mason
Lautz, Jonathan D.
Johnson, Richard S.
MacCoss, Michael J.
Smith, Stephen E. P.
author_sort Stillman, Mason
collection PubMed
description Neurons encode information by rapidly modifying synaptic protein complexes, which changes the strength of specific synaptic connections. Homer1 is abundantly expressed at glutamatergic synapses, and is known to alter its binding to metabotropic glutamate receptor 5 (mGlu5) in response to synaptic activity. However, Homer participates in many additional known interactions whose activity-dependence is unclear. Here, we used co-immunoprecipitation and label-free quantitative mass spectrometry to characterize activity-dependent interactions in the cerebral cortex of wildtype and Homer1 knockout mice. We identified a small, high-confidence protein network consisting of mGlu5, Shank2 and 3, and Homer1–3, of which only mGlu5 and Shank3 were significantly reduced following neuronal depolarization. We identified several other proteins that reduced their co-association in an activity-dependent manner, likely mediated by Shank proteins. We conclude that Homer1 dissociates from mGlu5 and Shank3 following depolarization, but our data suggest that direct Homer1 interactions in the cortex may be more limited than expected.
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spelling pubmed-88816022022-03-01 Activity dependent dissociation of the Homer1 interactome Stillman, Mason Lautz, Jonathan D. Johnson, Richard S. MacCoss, Michael J. Smith, Stephen E. P. Sci Rep Article Neurons encode information by rapidly modifying synaptic protein complexes, which changes the strength of specific synaptic connections. Homer1 is abundantly expressed at glutamatergic synapses, and is known to alter its binding to metabotropic glutamate receptor 5 (mGlu5) in response to synaptic activity. However, Homer participates in many additional known interactions whose activity-dependence is unclear. Here, we used co-immunoprecipitation and label-free quantitative mass spectrometry to characterize activity-dependent interactions in the cerebral cortex of wildtype and Homer1 knockout mice. We identified a small, high-confidence protein network consisting of mGlu5, Shank2 and 3, and Homer1–3, of which only mGlu5 and Shank3 were significantly reduced following neuronal depolarization. We identified several other proteins that reduced their co-association in an activity-dependent manner, likely mediated by Shank proteins. We conclude that Homer1 dissociates from mGlu5 and Shank3 following depolarization, but our data suggest that direct Homer1 interactions in the cortex may be more limited than expected. Nature Publishing Group UK 2022-02-25 /pmc/articles/PMC8881602/ /pubmed/35217690 http://dx.doi.org/10.1038/s41598-022-07179-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Stillman, Mason
Lautz, Jonathan D.
Johnson, Richard S.
MacCoss, Michael J.
Smith, Stephen E. P.
Activity dependent dissociation of the Homer1 interactome
title Activity dependent dissociation of the Homer1 interactome
title_full Activity dependent dissociation of the Homer1 interactome
title_fullStr Activity dependent dissociation of the Homer1 interactome
title_full_unstemmed Activity dependent dissociation of the Homer1 interactome
title_short Activity dependent dissociation of the Homer1 interactome
title_sort activity dependent dissociation of the homer1 interactome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8881602/
https://www.ncbi.nlm.nih.gov/pubmed/35217690
http://dx.doi.org/10.1038/s41598-022-07179-3
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