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

Anna Casanovas; Sara Salvany; Víctor Lahoz; Olga Tarabal; Lídia Piedrafita; Raimundo Sabater; Sara Hernandez; Jordi Calderó; Josep E. Esquerda

doi:10.1038/srep40155

journal article Open Access Jan 09, 2017

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

Anna Casanovas Sara Salvany Víctor Lahoz Olga Tarabal Lídia Piedrafita Raimundo Sabater Sara Hernandez Jordi Calderó Josep E. Esquerda

Scientific Reports Vol. 7 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/srep40155

Abstract

AbstractThe 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, Ca2+ 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.

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Published: Jan 09, 2017
Vol/Issue: 7(1)
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Authors

A

Anna Casanovas

Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina Institut de Recerca Biomèdica de Lleida (IRBLLEIDA), Universitat de Lleida Lleida Catalonia Spain

Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina Institut de Recerca Biomèdica de Lleida (IRBLLEIDA), Universitat de Lleida Lleida Catalonia Spain

L

Lídia Piedrafita

Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina Institut de Recerca Biomèdica de Lleida (IRBLLEIDA), Universitat de Lleida Lleida Catalonia Spain

Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina Institut de Recerca Biomèdica de Lleida (IRBLLEIDA), Universitat de Lleida Lleida Catalonia Spain

J

Josep E. Esquerda

Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina Institut de Recerca Biomèdica de Lleida (IRBLLEIDA), Universitat de Lleida Lleida Catalonia Spain

Cite This Article

Anna Casanovas, Sara Salvany, Víctor Lahoz, et al. (2017). Neuregulin 1-ErbB module in C-bouton synapses on somatic motor neurons: molecular compartmentation and response to peripheral nerve injury. Scientific Reports, 7(1). https://doi.org/10.1038/srep40155

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

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