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

Autor segons l'article: Salvany, Sara; Casanovas, Anna; Tarabal, Olga; Piedrafita, Lidia; Hernandez, Sara; Santafe, Manuel; Clara Soto-Bernardini, Maria; Caldero, Jordi; Schwab, Markus H; Esquerda, Josep E

Departament: Ciències Mèdiques Bàsiques

Autor/s de la URV: Santafé Martínez, Manuel

Paraules clau: Vacuoles; Tunicamycin; Thiourea; Terminals; Synapses; Subcellular fractions; Spinal motoneurons; Spinal cord; Signal transduction; Sigma-1 receptor; Sciatic nerve; Salubrinal; Protein isoforms; Presynaptic terminals; Nrg1 protein, mouse; Neuregulin-1; Nerve transection; Nerve regeneration; Nerve fibers, unmyelinated; Nerve crush; Motor neuron afferents; Microglia; Mice, transgenic; Mice; Interneurons; Expression; Endoplasmic-reticulum; Endoplasmic reticulum, smooth; Endoplasmic reticulum stress; Electric stimulation; Cinnamates; Cholinergic fibers; Channels; Cell-death; C-bouton; Axotomy; Anterior horn cells; Animals

Resum: 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.

Àrees temàtiques: 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

Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 08926638

Adreça de correu electrònic de l'autor: manuel.santafe@urv.cat

Data d'alta del registre: 2025-02-17

Versió de l'article dipositat: info:eu-repo/semantics/submittedVersion

Enllaç font original: https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201802329R

URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/

Referència a l'article segons font original: Faseb Journal. 33 (7): 7833-7851

Referència de l'ítem segons les normes APA: Salvany, Sara; Casanovas, Anna; Tarabal, Olga; Piedrafita, Lidia; Hernandez, Sara; Santafe, Manuel; Clara Soto-Bernardini, Maria; Caldero, Jordi; Schw (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

DOI de l'article: 10.1096/fj.201802329R

Entitat: Universitat Rovira i Virgili

Any de publicació de la revista: 2019

Tipus de publicació: Journal Publications