Cargando…

Neuregulin 1-ErbB module in C-bouton synapses on somatic motor neurons: molecular compartmentation and response to peripheral nerve injury

The electric activity of lower motor neurons (MNs) appears to play a role in determining cell-vulnerability in MN diseases. MN excitability is modulated by cholinergic inputs through C-type synaptic boutons, which display an endoplasmic reticulum-related subsurface cistern (SSC) adjacent to the post...

Descripción completa

Detalles Bibliográficos
Autores principales: Casanovas, Anna, Salvany, Sara, Lahoz, Víctor, Tarabal, Olga, Piedrafita, Lídia, Sabater, Raimundo, Hernández, Sara, Calderó, Jordi, Esquerda, Josep E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220293/
https://www.ncbi.nlm.nih.gov/pubmed/28065942
http://dx.doi.org/10.1038/srep40155
_version_ 1782492598319972352
author Casanovas, Anna
Salvany, Sara
Lahoz, Víctor
Tarabal, Olga
Piedrafita, Lídia
Sabater, Raimundo
Hernández, Sara
Calderó, Jordi
Esquerda, Josep E.
author_facet Casanovas, Anna
Salvany, Sara
Lahoz, Víctor
Tarabal, Olga
Piedrafita, Lídia
Sabater, Raimundo
Hernández, Sara
Calderó, Jordi
Esquerda, Josep E.
author_sort Casanovas, Anna
collection PubMed
description The electric activity of lower motor neurons (MNs) appears to play a role in determining cell-vulnerability in MN diseases. MN excitability is modulated by cholinergic inputs through C-type synaptic boutons, which display an endoplasmic reticulum-related subsurface cistern (SSC) adjacent to the postsynaptic membrane. Besides cholinergic molecules, a constellation of proteins involved in different signal-transduction pathways are clustered at C-type synaptic sites (M2 muscarinic receptors, Kv2.1 potassium channels, Ca(2+) activated K(+) [SK] channels, and sigma-1 receptors [S1R]), but their collective functional significance so far remains unknown. We have previously suggested that neuregulin-1 (NRG1)/ErbBs-based retrograde signalling occurs at this synapse. To better understand signalling through C-boutons, we performed an analysis of the distribution of C-bouton-associated signalling proteins. We show that within SSC, S1R, Kv2.1 and NRG1 are clustered in highly specific, non-overlapping, microdomains, whereas ErbB2 and ErbB4 are present in the adjacent presynaptic compartment. This organization may define highly ordered and spatially restricted sites for different signal-transduction pathways. SSC associated proteins are disrupted in axotomised MNs together with the activation of microglia, which display a positive chemotactism to C-bouton sites. This indicates that C-bouton associated molecules are also involved in neuroinflammatory signalling in diseased MNs, emerging as new potential therapeutic targets.
format Online
Article
Text
id pubmed-5220293
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-52202932017-01-11 Neuregulin 1-ErbB module in C-bouton synapses on somatic motor neurons: molecular compartmentation and response to peripheral nerve injury Casanovas, Anna Salvany, Sara Lahoz, Víctor Tarabal, Olga Piedrafita, Lídia Sabater, Raimundo Hernández, Sara Calderó, Jordi Esquerda, Josep E. Sci Rep Article The electric activity of lower motor neurons (MNs) appears to play a role in determining cell-vulnerability in MN diseases. MN excitability is modulated by cholinergic inputs through C-type synaptic boutons, which display an endoplasmic reticulum-related subsurface cistern (SSC) adjacent to the postsynaptic membrane. Besides cholinergic molecules, a constellation of proteins involved in different signal-transduction pathways are clustered at C-type synaptic sites (M2 muscarinic receptors, Kv2.1 potassium channels, Ca(2+) activated K(+) [SK] channels, and sigma-1 receptors [S1R]), but their collective functional significance so far remains unknown. We have previously suggested that neuregulin-1 (NRG1)/ErbBs-based retrograde signalling occurs at this synapse. To better understand signalling through C-boutons, we performed an analysis of the distribution of C-bouton-associated signalling proteins. We show that within SSC, S1R, Kv2.1 and NRG1 are clustered in highly specific, non-overlapping, microdomains, whereas ErbB2 and ErbB4 are present in the adjacent presynaptic compartment. This organization may define highly ordered and spatially restricted sites for different signal-transduction pathways. SSC associated proteins are disrupted in axotomised MNs together with the activation of microglia, which display a positive chemotactism to C-bouton sites. This indicates that C-bouton associated molecules are also involved in neuroinflammatory signalling in diseased MNs, emerging as new potential therapeutic targets. Nature Publishing Group 2017-01-09 /pmc/articles/PMC5220293/ /pubmed/28065942 http://dx.doi.org/10.1038/srep40155 Text en Copyright © 2017, The Author(s) 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
Casanovas, Anna
Salvany, Sara
Lahoz, Víctor
Tarabal, Olga
Piedrafita, Lídia
Sabater, Raimundo
Hernández, Sara
Calderó, Jordi
Esquerda, Josep E.
Neuregulin 1-ErbB module in C-bouton synapses on somatic motor neurons: molecular compartmentation and response to peripheral nerve injury
title Neuregulin 1-ErbB module in C-bouton synapses on somatic motor neurons: molecular compartmentation and response to peripheral nerve injury
title_full Neuregulin 1-ErbB module in C-bouton synapses on somatic motor neurons: molecular compartmentation and response to peripheral nerve injury
title_fullStr Neuregulin 1-ErbB module in C-bouton synapses on somatic motor neurons: molecular compartmentation and response to peripheral nerve injury
title_full_unstemmed Neuregulin 1-ErbB module in C-bouton synapses on somatic motor neurons: molecular compartmentation and response to peripheral nerve injury
title_short Neuregulin 1-ErbB module in C-bouton synapses on somatic motor neurons: molecular compartmentation and response to peripheral nerve injury
title_sort neuregulin 1-erbb module in c-bouton synapses on somatic motor neurons: molecular compartmentation and response to peripheral nerve injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220293/
https://www.ncbi.nlm.nih.gov/pubmed/28065942
http://dx.doi.org/10.1038/srep40155
work_keys_str_mv AT casanovasanna neuregulin1erbbmoduleincboutonsynapsesonsomaticmotorneuronsmolecularcompartmentationandresponsetoperipheralnerveinjury
AT salvanysara neuregulin1erbbmoduleincboutonsynapsesonsomaticmotorneuronsmolecularcompartmentationandresponsetoperipheralnerveinjury
AT lahozvictor neuregulin1erbbmoduleincboutonsynapsesonsomaticmotorneuronsmolecularcompartmentationandresponsetoperipheralnerveinjury
AT tarabalolga neuregulin1erbbmoduleincboutonsynapsesonsomaticmotorneuronsmolecularcompartmentationandresponsetoperipheralnerveinjury
AT piedrafitalidia neuregulin1erbbmoduleincboutonsynapsesonsomaticmotorneuronsmolecularcompartmentationandresponsetoperipheralnerveinjury
AT sabaterraimundo neuregulin1erbbmoduleincboutonsynapsesonsomaticmotorneuronsmolecularcompartmentationandresponsetoperipheralnerveinjury
AT hernandezsara neuregulin1erbbmoduleincboutonsynapsesonsomaticmotorneuronsmolecularcompartmentationandresponsetoperipheralnerveinjury
AT calderojordi neuregulin1erbbmoduleincboutonsynapsesonsomaticmotorneuronsmolecularcompartmentationandresponsetoperipheralnerveinjury
AT esquerdajosepe neuregulin1erbbmoduleincboutonsynapsesonsomaticmotorneuronsmolecularcompartmentationandresponsetoperipheralnerveinjury