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PLD1 participates in BDNF-induced signalling in cortical neurons

The brain-derived neurotrophic factor BDNF plays a critical role in neuronal development and the induction of L-LTP at glutamatergic synapses in several brain regions. However, the cellular and molecular mechanisms underlying these BDNF effects have not been firmly established. Using in vitro cultur...

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Detalles Bibliográficos
Autores principales: Ammar, Mohamed Raafet, Thahouly, Tamou, Hanauer, André, Stegner, David, Nieswandt, Bernhard, Vitale, Nicolas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594037/
https://www.ncbi.nlm.nih.gov/pubmed/26437780
http://dx.doi.org/10.1038/srep14778
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author Ammar, Mohamed Raafet
Thahouly, Tamou
Hanauer, André
Stegner, David
Nieswandt, Bernhard
Vitale, Nicolas
author_facet Ammar, Mohamed Raafet
Thahouly, Tamou
Hanauer, André
Stegner, David
Nieswandt, Bernhard
Vitale, Nicolas
author_sort Ammar, Mohamed Raafet
collection PubMed
description The brain-derived neurotrophic factor BDNF plays a critical role in neuronal development and the induction of L-LTP at glutamatergic synapses in several brain regions. However, the cellular and molecular mechanisms underlying these BDNF effects have not been firmly established. Using in vitro cultures of cortical neurons from knockout mice for Pld1 and Rsk2, BDNF was observed to induce a rapid RSK2-dependent activation of PLD and to stimulate BDNF ERK1/2-CREB and mTor-S6K signalling pathways, but these effects were greatly reduced in Pld1(−/−) neurons. Furthermore, phospho-CREB did not accumulate in the nucleus, whereas overexpression of PLD1 amplified the BDNF-dependent nuclear recruitment of phospho-ERK1/2 and phospho-CREB. This BDNF retrograde signalling was prevented in cells silenced for the scaffolding protein PEA15, a protein which complexes with PLD1, ERK1/2, and RSK2 after BDNF treatment. Finally PLD1, ERK1/2, and RSK2 partially colocalized on endosomal structures, suggesting that these proteins are part of the molecular module responsible for BDNF signalling in cortical neurons.
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spelling pubmed-45940372015-10-13 PLD1 participates in BDNF-induced signalling in cortical neurons Ammar, Mohamed Raafet Thahouly, Tamou Hanauer, André Stegner, David Nieswandt, Bernhard Vitale, Nicolas Sci Rep Article The brain-derived neurotrophic factor BDNF plays a critical role in neuronal development and the induction of L-LTP at glutamatergic synapses in several brain regions. However, the cellular and molecular mechanisms underlying these BDNF effects have not been firmly established. Using in vitro cultures of cortical neurons from knockout mice for Pld1 and Rsk2, BDNF was observed to induce a rapid RSK2-dependent activation of PLD and to stimulate BDNF ERK1/2-CREB and mTor-S6K signalling pathways, but these effects were greatly reduced in Pld1(−/−) neurons. Furthermore, phospho-CREB did not accumulate in the nucleus, whereas overexpression of PLD1 amplified the BDNF-dependent nuclear recruitment of phospho-ERK1/2 and phospho-CREB. This BDNF retrograde signalling was prevented in cells silenced for the scaffolding protein PEA15, a protein which complexes with PLD1, ERK1/2, and RSK2 after BDNF treatment. Finally PLD1, ERK1/2, and RSK2 partially colocalized on endosomal structures, suggesting that these proteins are part of the molecular module responsible for BDNF signalling in cortical neurons. Nature Publishing Group 2015-10-06 /pmc/articles/PMC4594037/ /pubmed/26437780 http://dx.doi.org/10.1038/srep14778 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ammar, Mohamed Raafet
Thahouly, Tamou
Hanauer, André
Stegner, David
Nieswandt, Bernhard
Vitale, Nicolas
PLD1 participates in BDNF-induced signalling in cortical neurons
title PLD1 participates in BDNF-induced signalling in cortical neurons
title_full PLD1 participates in BDNF-induced signalling in cortical neurons
title_fullStr PLD1 participates in BDNF-induced signalling in cortical neurons
title_full_unstemmed PLD1 participates in BDNF-induced signalling in cortical neurons
title_short PLD1 participates in BDNF-induced signalling in cortical neurons
title_sort pld1 participates in bdnf-induced signalling in cortical neurons
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594037/
https://www.ncbi.nlm.nih.gov/pubmed/26437780
http://dx.doi.org/10.1038/srep14778
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