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Synaptic activation of ribosomal protein S6 phosphorylation occurs locally in activated dendritic domains

Previous studies have shown that induction of long-term potentiation (LTP) induces phosphorylation of ribosomal protein S6 (rpS6) in postsynaptic neurons, but the functional significance of rpS6 phosphorylation is poorly understood. Here, we show that synaptic stimulation that induces perforant path...

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Detalles Bibliográficos
Autores principales: Pirbhoy, Patricia Salgado, Farris, Shannon, Steward, Oswald
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880148/
https://www.ncbi.nlm.nih.gov/pubmed/27194793
http://dx.doi.org/10.1101/lm.041947.116
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author Pirbhoy, Patricia Salgado
Farris, Shannon
Steward, Oswald
author_facet Pirbhoy, Patricia Salgado
Farris, Shannon
Steward, Oswald
author_sort Pirbhoy, Patricia Salgado
collection PubMed
description Previous studies have shown that induction of long-term potentiation (LTP) induces phosphorylation of ribosomal protein S6 (rpS6) in postsynaptic neurons, but the functional significance of rpS6 phosphorylation is poorly understood. Here, we show that synaptic stimulation that induces perforant path LTP triggers phosphorylation of rpS6 (p-rpS6) locally near active synapses. Using antibodies specific for phosphorylation at different sites (ser235/236 versus ser240/244), we show that strong synaptic activation led to dramatic increases in immunostaining throughout postsynaptic neurons with selectively higher staining for p-ser235/236 in the activated dendritic lamina. Following LTP induction, phosphorylation at ser235/236 was detectable by 5 min, peaked at 30 min, and was maintained for hours. Phosphorylation at both sites was completely blocked by local infusion of the NMDA receptor antagonist, APV. Despite robust induction of p-rpS6 following high frequency stimulation, assessment of protein synthesis by autoradiography revealed no detectable increases. Exploration of a novel environment led to increases in the number of p-rpS6-positive neurons throughout the forebrain in a pattern reminiscent of immediate early gene induction and many individual neurons that were p-rpS6-positive coexpressed Arc protein. Our results constrain hypotheses about the possible role of rpS6 phosphorylation in regulating postsynaptic protein synthesis during induction of synaptic plasticity.
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spelling pubmed-48801482017-06-01 Synaptic activation of ribosomal protein S6 phosphorylation occurs locally in activated dendritic domains Pirbhoy, Patricia Salgado Farris, Shannon Steward, Oswald Learn Mem Research Previous studies have shown that induction of long-term potentiation (LTP) induces phosphorylation of ribosomal protein S6 (rpS6) in postsynaptic neurons, but the functional significance of rpS6 phosphorylation is poorly understood. Here, we show that synaptic stimulation that induces perforant path LTP triggers phosphorylation of rpS6 (p-rpS6) locally near active synapses. Using antibodies specific for phosphorylation at different sites (ser235/236 versus ser240/244), we show that strong synaptic activation led to dramatic increases in immunostaining throughout postsynaptic neurons with selectively higher staining for p-ser235/236 in the activated dendritic lamina. Following LTP induction, phosphorylation at ser235/236 was detectable by 5 min, peaked at 30 min, and was maintained for hours. Phosphorylation at both sites was completely blocked by local infusion of the NMDA receptor antagonist, APV. Despite robust induction of p-rpS6 following high frequency stimulation, assessment of protein synthesis by autoradiography revealed no detectable increases. Exploration of a novel environment led to increases in the number of p-rpS6-positive neurons throughout the forebrain in a pattern reminiscent of immediate early gene induction and many individual neurons that were p-rpS6-positive coexpressed Arc protein. Our results constrain hypotheses about the possible role of rpS6 phosphorylation in regulating postsynaptic protein synthesis during induction of synaptic plasticity. Cold Spring Harbor Laboratory Press 2016-06 /pmc/articles/PMC4880148/ /pubmed/27194793 http://dx.doi.org/10.1101/lm.041947.116 Text en © 2016 Pirbhoy et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first 12 months after the full-issue publication date (see http://learnmem.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
Pirbhoy, Patricia Salgado
Farris, Shannon
Steward, Oswald
Synaptic activation of ribosomal protein S6 phosphorylation occurs locally in activated dendritic domains
title Synaptic activation of ribosomal protein S6 phosphorylation occurs locally in activated dendritic domains
title_full Synaptic activation of ribosomal protein S6 phosphorylation occurs locally in activated dendritic domains
title_fullStr Synaptic activation of ribosomal protein S6 phosphorylation occurs locally in activated dendritic domains
title_full_unstemmed Synaptic activation of ribosomal protein S6 phosphorylation occurs locally in activated dendritic domains
title_short Synaptic activation of ribosomal protein S6 phosphorylation occurs locally in activated dendritic domains
title_sort synaptic activation of ribosomal protein s6 phosphorylation occurs locally in activated dendritic domains
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880148/
https://www.ncbi.nlm.nih.gov/pubmed/27194793
http://dx.doi.org/10.1101/lm.041947.116
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