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AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity

AKT is a kinase regulating numerous cellular processes in the brain, and mutations in AKT are known to affect brain function. AKT is indirectly implicated in synaptic plasticity, but its direct role has not been studied. Moreover, three highly related AKT isoforms are expressed in the brain, but the...

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Autores principales: Levenga, Josien, Wong, Helen, Milstead, Ryan A, Keller, Bailey N, LaPlante, Lauren E, Hoeffer, Charles A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722612/
https://www.ncbi.nlm.nih.gov/pubmed/29173281
http://dx.doi.org/10.7554/eLife.30640
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author Levenga, Josien
Wong, Helen
Milstead, Ryan A
Keller, Bailey N
LaPlante, Lauren E
Hoeffer, Charles A
author_facet Levenga, Josien
Wong, Helen
Milstead, Ryan A
Keller, Bailey N
LaPlante, Lauren E
Hoeffer, Charles A
author_sort Levenga, Josien
collection PubMed
description AKT is a kinase regulating numerous cellular processes in the brain, and mutations in AKT are known to affect brain function. AKT is indirectly implicated in synaptic plasticity, but its direct role has not been studied. Moreover, three highly related AKT isoforms are expressed in the brain, but their individual roles are poorly understood. We find in Mus musculus, each AKT isoform has a unique expression pattern in the hippocampus, with AKT1 and AKT3 primarily in neurons but displaying local differences, while AKT2 is in astrocytes. We also find isoform-specific roles for AKT in multiple paradigms of hippocampal synaptic plasticity in area CA1. AKT1, but not AKT2 or AKT3, is required for L-LTP through regulating activity-induced protein synthesis. Interestingly, AKT activity inhibits mGluR-LTD, with overlapping functions for AKT1 and AKT3. In summary, our studies identify distinct expression patterns and roles in synaptic plasticity for AKT isoforms in the hippocampus.
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spelling pubmed-57226122017-12-11 AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity Levenga, Josien Wong, Helen Milstead, Ryan A Keller, Bailey N LaPlante, Lauren E Hoeffer, Charles A eLife Cell Biology AKT is a kinase regulating numerous cellular processes in the brain, and mutations in AKT are known to affect brain function. AKT is indirectly implicated in synaptic plasticity, but its direct role has not been studied. Moreover, three highly related AKT isoforms are expressed in the brain, but their individual roles are poorly understood. We find in Mus musculus, each AKT isoform has a unique expression pattern in the hippocampus, with AKT1 and AKT3 primarily in neurons but displaying local differences, while AKT2 is in astrocytes. We also find isoform-specific roles for AKT in multiple paradigms of hippocampal synaptic plasticity in area CA1. AKT1, but not AKT2 or AKT3, is required for L-LTP through regulating activity-induced protein synthesis. Interestingly, AKT activity inhibits mGluR-LTD, with overlapping functions for AKT1 and AKT3. In summary, our studies identify distinct expression patterns and roles in synaptic plasticity for AKT isoforms in the hippocampus. eLife Sciences Publications, Ltd 2017-11-27 /pmc/articles/PMC5722612/ /pubmed/29173281 http://dx.doi.org/10.7554/eLife.30640 Text en © 2017, Levenga et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Levenga, Josien
Wong, Helen
Milstead, Ryan A
Keller, Bailey N
LaPlante, Lauren E
Hoeffer, Charles A
AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity
title AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity
title_full AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity
title_fullStr AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity
title_full_unstemmed AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity
title_short AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity
title_sort akt isoforms have distinct hippocampal expression and roles in synaptic plasticity
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722612/
https://www.ncbi.nlm.nih.gov/pubmed/29173281
http://dx.doi.org/10.7554/eLife.30640
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