Neuregulin-1 is concentrated in the postsynaptic subsurface cistern of C-bouton inputs to alpha-motoneurons and altered during motoneuron diseases

作者：Gallart Palau Xavier; Tarabal Olga; Casanovas Anna; Sabado Javier; Correa Francisco J; Hereu Marta; Piedrafita Lidia; Caldero Jordi^*; Esquerda Josep E

来源：The FASEB Journal, 2014, 28(8): 3618-3632.

DOI：10.1096/fj.13-248583

• spinal cord ventral horn
• interneurons
• erbB receptors
• spinal muscular atrophy
• amyotrophic lateral sclerosis

C boutons are large, cholinergic, synaptic terminals that arise from local interneurons and specifically contact spinal alpha-motoneurons (MNs). C boutons characteristically display a postsynaptic specialization consisting of an endoplasmic reticulum-related subsurface cistern (SSC) of unknown function. In the present work, by using confocal microscopy and ultrastructural immunolabeling, we demonstrate that neuregulin-1 (NRG1) accumulates in the SSC of mouse spinal MNs. We also show that the NRG1 receptors erbB2 and erbB4 are presynaptically localized within C boutons, suggesting that NRG1-based retrograde signaling may occur in this type of synapse. In most of the cranial nuclei, MNs display the same pattern of NRG1 distribution as that observed in spinal cord MNs. Conversely, MNs in oculomotor nuclei, which are spared in amyotrophic lateral sclerosis (ALS), lack both C boutons and SSC-associated NRG1. NRG1 in spinal MNs is developmentally regulated and depends on the maintenance of nerve-muscle interactions, as we show after nerve transection experiments. Changes in NRG1 in C boutons were also investigated in mouse models of MN diseases: i.e., spinal muscular atrophy (SMN Delta 7) and ALS (SOD1(G93A)). In both models, a transient increase in NRG1 in C boutons occurs during disease progression. These data increase our understanding of the role of C boutons in MN physiology and pathology.-Gallart-Palau, X., Tarabal, O., Casanovas, A., S bado, J., Correa, F. J., Hereu, M., Piedrafita, L., Calder, J., Esquerda, J. E. Neuregulin-1 is concentrated in the postsynaptic subsurface cistern of C-bouton inputs to alpha-motoneurons and altered during motoneuron diseases.

• 出版日期2014-8