Author, as appears in the article.: Salvany S, Casanovas A, Tarabal O, Piedrafita L, Hernández S, Santafé M, Soto-Bernardini MC, Calderó J, Schwab MH, Esquerda JE

Department: Ciències Mèdiques Bàsiques

URV's Author/s: Santafé Martínez, Manuel

Keywords: Terminals Synapses Spinal motoneurons Spinal cord Sigma-1 receptor Nerve transection Motor neuron afferents Microglia Mice Interneurons Expression Endoplasmic-reticulum Channels Cell-death C-bouton

Abstract: C-type synaptic boutons (C-boutons) provide cholinergic afferent input to spinal cord motor neurons (MNs), which display an endoplasmic reticulum (ER)-related subsurface cistern (SSC) adjacent to their postsynaptic membrane. A constellation of postsynaptic proteins is clustered at C-boutons, including M2 muscarinic receptors, potassium channels, and σ-1 receptors. In addition, we previously found that neuregulin (NRG)1 is associated with C-boutons at postsynaptic SSCs, whereas its ErbB receptors are located in the presynaptic compartment. C-bouton-mediated regulation of MN excitability has been implicated in MN disease, but NRG1-mediated functions and the impact of various pathologic conditions on C-bouton integrity have not been studied in detail. Here, we investigated changes in C-boutons after electrical stimulation, pharmacological treatment, and peripheral nerve axotomy. SSC-linked NRG1 clusters were severely disrupted in acutely stressed MNs and after tunicamycin-induced ER stress. In axotomized MNs, C-bouton loss occurred in concomitance with microglial recruitment and was prevented by the ER stress inhibitor salubrinal. Activated microglia displayed a positive chemotaxis to C-boutons. Analysis of transgenic mice overexpressing NRG1 type I and type III isoforms in MNs indicated that NRG1 type III acts as an organizer of SSC-like structures, whereas NRG1 type I promotes synaptogenesis of presynaptic cholinergic terminals. Moreover, MN-derived NRG1 signals may regulate the activity of perineuronal microglial cells. Together, these data provide new insights into the molecular and cellular pathology of C-boutons in MN injury and suggest that distinct NRG1 isoform-mediated signaling functions regulate the complex matching between pre- and postsynaptic C-bouton elements.-Salvany, S., Casanovas, A., Tarabal, O., Piedrafita, L., Hernández, S., Santafé, M., Soto-Bernardini, M. C., Calderó, J., Schwab, M. H., Esquerda, J. E. Localization and dynamic changes of neuregulin-1 at C-type synaptic boutons in association with motor neuron injury and repair.

Thematic Areas: Saúde coletiva Química Psicología Odontología Nutrição Molecular biology Medicine (miscellaneous) Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar Genetics General medicine Farmacia Engenharias iv Engenharias ii Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Cell biology Biotecnología Biotechnology Biology Biodiversidade Biochemistry & molecular biology Biochemistry Astronomia / física

licence for use: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 08926638

Author's mail: manuel.santafe@urv.cat

Author identifier: 0000-0002-5462-5108

Record's date: 2023-02-18

Papper version: info:eu-repo/semantics/submittedVersion

Link to the original source: https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201802329R

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Faseb Journal. 33 (7): 7833-7851

APA: Salvany S, Casanovas A, Tarabal O, Piedrafita L, Hernández S, Santafé M, Soto-Bernardini MC, Calderó J, Schwab MH, Esquerda JE (2019). Localization and dynamic changes of neuregulin-1 at C-type synaptic boutons in association with motor neuron injury and repair. Faseb Journal, 33(7), 7833-7851. DOI: 10.1096/fj.201802329R

Article's DOI: 10.1096/fj.201802329R

Entity: Universitat Rovira i Virgili

Journal publication year: 2019

Publication Type: Journal Publications