The p38(MAPK)-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission

p38 is a mitogen-activated protein kinase (MAPK), that responds primarily to stress stimuli. p38 has a number of targets for phosphorylation, including MAPK-activated protein kinase 2 (MK2). MK2 primarily functions as a master regulator of RNA-binding proteins, indirectly controlling gene expression...

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Autores principales: Beamer, Edward, Corrêa, Sonia A. L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876405/
https://www.ncbi.nlm.nih.gov/pubmed/33585492
http://dx.doi.org/10.3389/fcell.2021.635636
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author Beamer, Edward
Corrêa, Sonia A. L.
author_facet Beamer, Edward
Corrêa, Sonia A. L.
author_sort Beamer, Edward
collection PubMed
description p38 is a mitogen-activated protein kinase (MAPK), that responds primarily to stress stimuli. p38 has a number of targets for phosphorylation, including MAPK-activated protein kinase 2 (MK2). MK2 primarily functions as a master regulator of RNA-binding proteins, indirectly controlling gene expression at the level of translation. The role of MK2 in regulating the synthesis of pro-inflammatory cytokines downstream of inflammation and cellular stress is well-described. A significant amount of evidence, however, now points to a role for the p38(MAPK)-MK2 signaling axis in mediating synaptic plasticity through control of AMPA receptor trafficking and the morphology of dendritic spines. These processes are mediated through control of cytoskeletal dynamics via the activation of cofilin-1 and possibly control of the expression of Arc/Arg3.1. There is evidence that MK2 is necessary for group I metabotropic glutamate receptors long-term depression (mGluR-LTD). Disruption of this signaling may play an important role in mediating cognitive dysfunction in neurological disorders such as fragile X syndrome and Alzheimer’s disease. To date, the role of neuronal MK2 mediating synaptic plasticity in response to inflammatory stimuli has not yet been investigated. In immune cells, it is clear that MK2 is phosphorylated following activation of a broad range of cell surface receptors for cytokines and other inflammatory mediators. We propose that neuronal MK2 may be an important player in the link between inflammatory states and dysregulation of synaptic plasticity underlying cognitive functions. Finally, we discuss the potential of the p38(MAPK)-MK2 signaling axis as target for therapeutic intervention in a number of neurological disorders.
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spelling pubmed-78764052021-02-12 The p38(MAPK)-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission Beamer, Edward Corrêa, Sonia A. L. Front Cell Dev Biol Cell and Developmental Biology p38 is a mitogen-activated protein kinase (MAPK), that responds primarily to stress stimuli. p38 has a number of targets for phosphorylation, including MAPK-activated protein kinase 2 (MK2). MK2 primarily functions as a master regulator of RNA-binding proteins, indirectly controlling gene expression at the level of translation. The role of MK2 in regulating the synthesis of pro-inflammatory cytokines downstream of inflammation and cellular stress is well-described. A significant amount of evidence, however, now points to a role for the p38(MAPK)-MK2 signaling axis in mediating synaptic plasticity through control of AMPA receptor trafficking and the morphology of dendritic spines. These processes are mediated through control of cytoskeletal dynamics via the activation of cofilin-1 and possibly control of the expression of Arc/Arg3.1. There is evidence that MK2 is necessary for group I metabotropic glutamate receptors long-term depression (mGluR-LTD). Disruption of this signaling may play an important role in mediating cognitive dysfunction in neurological disorders such as fragile X syndrome and Alzheimer’s disease. To date, the role of neuronal MK2 mediating synaptic plasticity in response to inflammatory stimuli has not yet been investigated. In immune cells, it is clear that MK2 is phosphorylated following activation of a broad range of cell surface receptors for cytokines and other inflammatory mediators. We propose that neuronal MK2 may be an important player in the link between inflammatory states and dysregulation of synaptic plasticity underlying cognitive functions. Finally, we discuss the potential of the p38(MAPK)-MK2 signaling axis as target for therapeutic intervention in a number of neurological disorders. Frontiers Media S.A. 2021-01-28 /pmc/articles/PMC7876405/ /pubmed/33585492 http://dx.doi.org/10.3389/fcell.2021.635636 Text en Copyright © 2021 Beamer and Corrêa. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Beamer, Edward
Corrêa, Sonia A. L.
The p38(MAPK)-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission
title The p38(MAPK)-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission
title_full The p38(MAPK)-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission
title_fullStr The p38(MAPK)-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission
title_full_unstemmed The p38(MAPK)-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission
title_short The p38(MAPK)-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission
title_sort p38(mapk)-mk2 signaling axis as a critical link between inflammation and synaptic transmission
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876405/
https://www.ncbi.nlm.nih.gov/pubmed/33585492
http://dx.doi.org/10.3389/fcell.2021.635636
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