Articles producció científica> Ciències Mèdiques Bàsiques

Localization and dynamic changes of neuregulin-1 at C-type synaptic boutons in association with motor neuron injury and repair

  • Identification data

    Identifier: imarina:5873673
    Authors:
    Salvany S, Casanovas A, Tarabal O, Piedrafita L, Hernández S, Santafé M, Soto-Bernardini MC, Calderó J, Schwab MH, Esquerda JE
    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 element
  • Others:

    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
    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
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Article's DOI: 10.1096/fj.201802329R
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2019
    Publication Type: Journal Publications
  • Keywords:

    Biochemistry,Biochemistry & Molecular Biology,Biology,Biotechnology,Cell Biology,Genetics,Medicine (Miscellaneous),Molecular Biology
    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
    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
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