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Mice lacking the cAMP effector protein POPDC1 show enhanced hippocampal synaptic plasticity
Extensive research has uncovered diverse forms of synaptic plasticity and an array of molecular signaling mechanisms that act as positive or negative regulators. Specifically, cyclic 3′,5′-cyclic adenosine monophosphate (cAMP)-dependent signaling pathways are crucially implicated in long-lasting syn...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376866/ https://www.ncbi.nlm.nih.gov/pubmed/34937090 http://dx.doi.org/10.1093/cercor/bhab426 |
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author | Shetty, Mahesh Shivarama Ris, Laurence Schindler, Roland F R Mizuno, Keiko Fedele, Laura Giese, Karl Peter Brand, Thomas Abel, Ted |
author_facet | Shetty, Mahesh Shivarama Ris, Laurence Schindler, Roland F R Mizuno, Keiko Fedele, Laura Giese, Karl Peter Brand, Thomas Abel, Ted |
author_sort | Shetty, Mahesh Shivarama |
collection | PubMed |
description | Extensive research has uncovered diverse forms of synaptic plasticity and an array of molecular signaling mechanisms that act as positive or negative regulators. Specifically, cyclic 3′,5′-cyclic adenosine monophosphate (cAMP)-dependent signaling pathways are crucially implicated in long-lasting synaptic plasticity. In this study, we examine the role of Popeye domain-containing protein 1 (POPDC1) (or blood vessel epicardial substance (BVES)), a cAMP effector protein, in modulating hippocampal synaptic plasticity. Unlike other cAMP effectors, such as protein kinase A (PKA) and exchange factor directly activated by cAMP, POPDC1 is membrane-bound and the sequence of the cAMP-binding cassette differs from canonical cAMP-binding domains, suggesting that POPDC1 may have an unique role in cAMP-mediated signaling. Our results show that Popdc1 is widely expressed in various brain regions including the hippocampus. Acute hippocampal slices from Popdc1 knockout (KO) mice exhibit PKA-dependent enhancement in CA1 long-term potentiation (LTP) in response to weaker stimulation paradigms, which in slices from wild-type mice induce only transient LTP. Loss of POPDC1, while not affecting basal transmission or input-specificity of LTP, results in altered response during high-frequency stimulation. Popdc1 KO mice also show enhanced forskolin-induced potentiation. Overall, these findings reveal POPDC1 as a novel negative regulator of hippocampal synaptic plasticity and, together with recent evidence for its interaction with phosphodiesterases (PDEs), suggest that POPDC1 is involved in modulating activity-dependent local cAMP–PKA–PDE signaling. |
format | Online Article Text |
id | pubmed-9376866 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-93768662022-08-16 Mice lacking the cAMP effector protein POPDC1 show enhanced hippocampal synaptic plasticity Shetty, Mahesh Shivarama Ris, Laurence Schindler, Roland F R Mizuno, Keiko Fedele, Laura Giese, Karl Peter Brand, Thomas Abel, Ted Cereb Cortex Original Article Extensive research has uncovered diverse forms of synaptic plasticity and an array of molecular signaling mechanisms that act as positive or negative regulators. Specifically, cyclic 3′,5′-cyclic adenosine monophosphate (cAMP)-dependent signaling pathways are crucially implicated in long-lasting synaptic plasticity. In this study, we examine the role of Popeye domain-containing protein 1 (POPDC1) (or blood vessel epicardial substance (BVES)), a cAMP effector protein, in modulating hippocampal synaptic plasticity. Unlike other cAMP effectors, such as protein kinase A (PKA) and exchange factor directly activated by cAMP, POPDC1 is membrane-bound and the sequence of the cAMP-binding cassette differs from canonical cAMP-binding domains, suggesting that POPDC1 may have an unique role in cAMP-mediated signaling. Our results show that Popdc1 is widely expressed in various brain regions including the hippocampus. Acute hippocampal slices from Popdc1 knockout (KO) mice exhibit PKA-dependent enhancement in CA1 long-term potentiation (LTP) in response to weaker stimulation paradigms, which in slices from wild-type mice induce only transient LTP. Loss of POPDC1, while not affecting basal transmission or input-specificity of LTP, results in altered response during high-frequency stimulation. Popdc1 KO mice also show enhanced forskolin-induced potentiation. Overall, these findings reveal POPDC1 as a novel negative regulator of hippocampal synaptic plasticity and, together with recent evidence for its interaction with phosphodiesterases (PDEs), suggest that POPDC1 is involved in modulating activity-dependent local cAMP–PKA–PDE signaling. Oxford University Press 2021-12-23 /pmc/articles/PMC9376866/ /pubmed/34937090 http://dx.doi.org/10.1093/cercor/bhab426 Text en © The Author(s) 2021. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Shetty, Mahesh Shivarama Ris, Laurence Schindler, Roland F R Mizuno, Keiko Fedele, Laura Giese, Karl Peter Brand, Thomas Abel, Ted Mice lacking the cAMP effector protein POPDC1 show enhanced hippocampal synaptic plasticity |
title | Mice lacking the cAMP effector protein POPDC1 show enhanced hippocampal synaptic plasticity |
title_full | Mice lacking the cAMP effector protein POPDC1 show enhanced hippocampal synaptic plasticity |
title_fullStr | Mice lacking the cAMP effector protein POPDC1 show enhanced hippocampal synaptic plasticity |
title_full_unstemmed | Mice lacking the cAMP effector protein POPDC1 show enhanced hippocampal synaptic plasticity |
title_short | Mice lacking the cAMP effector protein POPDC1 show enhanced hippocampal synaptic plasticity |
title_sort | mice lacking the camp effector protein popdc1 show enhanced hippocampal synaptic plasticity |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376866/ https://www.ncbi.nlm.nih.gov/pubmed/34937090 http://dx.doi.org/10.1093/cercor/bhab426 |
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