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Aβ-induced synaptic impairments require CaMKII activity that is stimulated by indirect signaling events
Aβ bears homology to the CaMKII regulatory domain, and peptides derived from this domain can bind and disrupt the CaMKII holoenzyme, suggesting that Aβ could have a similar effect. Notably, Aβ impairs the synaptic CaMKII accumulation that is mediated by GluN2B binding, which requires CaMKII assembly...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127195/ https://www.ncbi.nlm.nih.gov/pubmed/35620430 http://dx.doi.org/10.1016/j.isci.2022.104368 |
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author | Brown, Carolyn Nicole Rumian, Nicole L. Tullis, Jonathan E. Coultrap, Steven J. Bayer, K. Ulrich |
author_facet | Brown, Carolyn Nicole Rumian, Nicole L. Tullis, Jonathan E. Coultrap, Steven J. Bayer, K. Ulrich |
author_sort | Brown, Carolyn Nicole |
collection | PubMed |
description | Aβ bears homology to the CaMKII regulatory domain, and peptides derived from this domain can bind and disrupt the CaMKII holoenzyme, suggesting that Aβ could have a similar effect. Notably, Aβ impairs the synaptic CaMKII accumulation that is mediated by GluN2B binding, which requires CaMKII assembly into holoenzymes. Furthermore, this Aβ-induced impairment is prevented by CaMKII inhibitors that should also inhibit the putative direct Aβ binding. However, our study did not find any evidence for direct effects of Aβ on CaMKII: Aβ did not directly disrupt CaMKII holoenzymes, GluN2B binding, T286 autophosphorylation, or kinase activity in vitro. Most importantly, in neurons, the Aβ-induced impairment of CaMKII synaptic accumulation was prevented by an ATP-competitive CaMKII inhibitor that would not interfere with the putative direct Aβ binding. Together, our results indicate that synaptic Aβ effects are not mediated by direct binding to CaMKII, but instead require CaMKII activation via indirect signaling events. |
format | Online Article Text |
id | pubmed-9127195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-91271952022-05-25 Aβ-induced synaptic impairments require CaMKII activity that is stimulated by indirect signaling events Brown, Carolyn Nicole Rumian, Nicole L. Tullis, Jonathan E. Coultrap, Steven J. Bayer, K. Ulrich iScience Article Aβ bears homology to the CaMKII regulatory domain, and peptides derived from this domain can bind and disrupt the CaMKII holoenzyme, suggesting that Aβ could have a similar effect. Notably, Aβ impairs the synaptic CaMKII accumulation that is mediated by GluN2B binding, which requires CaMKII assembly into holoenzymes. Furthermore, this Aβ-induced impairment is prevented by CaMKII inhibitors that should also inhibit the putative direct Aβ binding. However, our study did not find any evidence for direct effects of Aβ on CaMKII: Aβ did not directly disrupt CaMKII holoenzymes, GluN2B binding, T286 autophosphorylation, or kinase activity in vitro. Most importantly, in neurons, the Aβ-induced impairment of CaMKII synaptic accumulation was prevented by an ATP-competitive CaMKII inhibitor that would not interfere with the putative direct Aβ binding. Together, our results indicate that synaptic Aβ effects are not mediated by direct binding to CaMKII, but instead require CaMKII activation via indirect signaling events. Elsevier 2022-05-06 /pmc/articles/PMC9127195/ /pubmed/35620430 http://dx.doi.org/10.1016/j.isci.2022.104368 Text en © 2022 The Authors https://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 Brown, Carolyn Nicole Rumian, Nicole L. Tullis, Jonathan E. Coultrap, Steven J. Bayer, K. Ulrich Aβ-induced synaptic impairments require CaMKII activity that is stimulated by indirect signaling events |
title | Aβ-induced synaptic impairments require CaMKII activity that is stimulated by indirect signaling events |
title_full | Aβ-induced synaptic impairments require CaMKII activity that is stimulated by indirect signaling events |
title_fullStr | Aβ-induced synaptic impairments require CaMKII activity that is stimulated by indirect signaling events |
title_full_unstemmed | Aβ-induced synaptic impairments require CaMKII activity that is stimulated by indirect signaling events |
title_short | Aβ-induced synaptic impairments require CaMKII activity that is stimulated by indirect signaling events |
title_sort | aβ-induced synaptic impairments require camkii activity that is stimulated by indirect signaling events |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127195/ https://www.ncbi.nlm.nih.gov/pubmed/35620430 http://dx.doi.org/10.1016/j.isci.2022.104368 |
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