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A constellation of postsynaptic proteins is clustered at C\u2010boutons, including M2 muscarinic receptors, potassium channels, and \u03c3\u20101 receptors. In addition, we previously found that neuregulin (NRG)1 is associated with C\u2010boutons at postsynaptic SSCs, whereas its ErbB receptors are located in the presynaptic compartment. C\u2010bouton\u2013mediated regulation of MN excitability has been implicated in MN disease, but NRG1\u2010mediated functions and the impact of various pathologic conditions on C\u2010bouton integrity have not been studied in detail. Here, we investigated changes in C\u2010boutons after electrical stimulation, pharmacological treatment, and peripheral nerve axotomy. SSC\u2010linked NRG1 clusters were severely disrupted in acutely stressed MNs and after tunicamycin\u2010induced ER stress. In axotomized MNs, C\u2010bouton loss occurred in concomitance with microglial recruitment and was prevented by the ER stress inhibitor salubrinal. Activated microglia displayed a positive chemotaxis to C\u2010boutons. 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\u2010like structures, whereas NRG1 type I promotes synaptogenesis of presynaptic cholinergic terminals. Moreover, MN\u2010derived NRG1 signals may regulate the activity of perineuronal microglial cells. Together, these data provide new insights into the molecular and cellular pathology of C\u2010boutons in MN injury and suggest that distinct NRG1 isoform\u2013mediated signaling functions regulate the complex matching between pre\u2010 and postsynaptic C\u2010bouton elements.\u2014Salvany, S., Casanovas, A., Tarabal, O., Piedrafita, L., Hern\u00e1ndez, S., Santaf\u00e9, M., Soto\u2010Bernardini, M. C., Calder\u00f3, J., Schwab, M. H., Esquerda, J. E. Localization and dynamic changes of neuregulin\u20101 at C\u2010type synaptic boutons in association with motor neuron injury and repair. FASEB J. 33, 7833\u20137851 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201802329r","type":"journal-article","created":{"date-parts":[[2019,3,26]],"date-time":"2019-03-26T16:21:47Z","timestamp":1553617307000},"page":"7833-7851","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Localization and dynamic changes of neuregulin\u20101 at C\u2010type synaptic boutons in association with motor neuron injury and repair"],"prefix":"10.1096","volume":"33","author":[{"given":"Sara","family":"Salvany","sequence":"first","affiliation":[{"name":"Unitat de Neurobiologia Cellular Departament de Medicina Experimental Facultat de Medicina Universitat de Lleida\u2013Institut de Recerca Biom\u00e8dica de Lleida (IRBLLEIDA)  Lleida Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Casanovas","sequence":"additional","affiliation":[{"name":"Unitat de Neurobiologia Cellular Departament de Medicina Experimental Facultat de Medicina Universitat de Lleida\u2013Institut de Recerca Biom\u00e8dica de Lleida (IRBLLEIDA)  Lleida Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Tarabal","sequence":"additional","affiliation":[{"name":"Unitat de Neurobiologia Cellular Departament de Medicina Experimental Facultat de Medicina Universitat de Lleida\u2013Institut de Recerca Biom\u00e8dica de Lleida (IRBLLEIDA)  Lleida Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00eddia","family":"Piedrafita","sequence":"additional","affiliation":[{"name":"Unitat de Neurobiologia Cellular Departament de Medicina Experimental Facultat de Medicina Universitat de Lleida\u2013Institut de Recerca Biom\u00e8dica de Lleida (IRBLLEIDA)  Lleida Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Unitat de Neurobiologia Cellular Departament de Medicina Experimental Facultat de Medicina Universitat de Lleida\u2013Institut de Recerca Biom\u00e8dica de Lleida (IRBLLEIDA)  Lleida Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Santaf\u00e9","sequence":"additional","affiliation":[{"name":"Unitat d'Histologia i Neurobiologia (UHN) Facultat de Medicina i Ci\u00e8ncies de la Salut Universitat Rovira i Virgili  Reus Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Clara","family":"Soto-Bernardini","sequence":"additional","affiliation":[{"name":"Instituto Tecnol\u00f3gico de Costa Rica (TEC) Centro de Investigaci\u00f3n en Biotecnolog\u00eda (CIB) Escuela de Biolog\u00eda  Cartago Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Calder\u00f3","sequence":"additional","affiliation":[{"name":"Unitat de Neurobiologia Cellular Departament de Medicina Experimental Facultat de Medicina Universitat de Lleida\u2013Institut de Recerca Biom\u00e8dica de Lleida (IRBLLEIDA)  Lleida Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus H.","family":"Schwab","sequence":"additional","affiliation":[{"name":"Institute of Cellular Neurophysiology Hannover Medical School  Hannover Germany"},{"name":"Center for Systems Neuroscience (ZSN) University of Veterinary Medicine Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep E.","family":"Esquerda","sequence":"additional","affiliation":[{"name":"Instituto Tecnol\u00f3gico de Costa Rica (TEC) Centro de Investigaci\u00f3n en Biotecnolog\u00eda (CIB) Escuela de Biolog\u00eda  Cartago Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.2.767"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.051508.135722"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611134104"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.10.017"},{"key":"e_1_2_9_6_1","first-page":"85","article-title":"Ultrastructure of dorsal root boutons on lumbosacral motoneurons of the adult cat, as revealed by dorsal root section","volume":"332","author":"Conradi S.","year":"1969","journal-title":"Acta Physiol. 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