Silencing rapsyn in vivo decreases acetylcholine receptors and augments sodium channels and secondary postsynaptic membrane folding
The receptor-associated protein of the synapse (rapsyn) is required for anchoring and stabilizing the nicotinic acetylcholine receptor (AChR) in the postsynaptic membrane of the neuromuscular junction (NMJ) during development. Here we studied the role of rapsyn in the maintenance of the adult NMJ by...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2009-07-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999610900059X |
| _version_ | 1818724674251522048 |
|---|---|
| author | Pilar Martínez-Martínez Marko Phernambucq Laura Steinbusch Laurent Schaeffer Sonia Berrih-Aknin Hans Duimel Peter Frederik Peter Molenaar Marc H. De Baets Mario Losen |
| author_facet | Pilar Martínez-Martínez Marko Phernambucq Laura Steinbusch Laurent Schaeffer Sonia Berrih-Aknin Hans Duimel Peter Frederik Peter Molenaar Marc H. De Baets Mario Losen |
| author_sort | Pilar Martínez-Martínez |
| collection | DOAJ |
| description | The receptor-associated protein of the synapse (rapsyn) is required for anchoring and stabilizing the nicotinic acetylcholine receptor (AChR) in the postsynaptic membrane of the neuromuscular junction (NMJ) during development. Here we studied the role of rapsyn in the maintenance of the adult NMJ by reducing rapsyn expression levels with short hairpin RNA (shRNA). Silencing rapsyn led to the average reduction of the protein levels of rapsyn (31% loss) and AChR (36% loss) at the NMJ within 2 weeks, corresponding to previously reported half life of these proteins. On the other hand, the sodium channel protein expression was augmented (66%) in rapsyn-silenced muscles. Unexpectedly, at the ultrastructural level a significant increase in the amount of secondary folds of the postsynaptic membrane in silenced muscles was observed. The neuromuscular transmission in rapsyn-silenced muscles was mildly impaired. The results suggest that the adult NMJ can rapidly produce postsynaptic folds to compensate for AChR and rapsyn loss. |
| first_indexed | 2024-12-17T21:30:10Z |
| format | Article |
| id | doaj.art-5f3c19b4f7b344d481c9d145fb4241a2 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T21:30:10Z |
| publishDate | 2009-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-5f3c19b4f7b344d481c9d145fb4241a22022-12-21T21:31:55ZengElsevierNeurobiology of Disease1095-953X2009-07-013511423Silencing rapsyn in vivo decreases acetylcholine receptors and augments sodium channels and secondary postsynaptic membrane foldingPilar Martínez-Martínez0Marko Phernambucq1Laura Steinbusch2Laurent Schaeffer3Sonia Berrih-Aknin4Hans Duimel5Peter Frederik6Peter Molenaar7Marc H. De Baets8Mario Losen9Department of Neuroscience, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands, PO Box 616, 6200 MD Maastricht, The Netherlands; Corresponding author. Fax: +31 43 3671096.Department of Neuroscience, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands, PO Box 616, 6200 MD Maastricht, The NetherlandsDepartment of Neuroscience, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands, PO Box 616, 6200 MD Maastricht, The NetherlandsÉquipe Différenciation Neuromusculaire, Institut Fédératif de Recherche 128, Unité Mixte de Recherche 5161, Centre National de la Recherche Scientifique; École Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon Cedex 07, FranceCNRS-UMR 8162, IPSC, Université Paris XI, Hôpital Marie Lannelongue, FranceElectron Microscopy Unit, Department of Pathology, Maastricht University, Maastricht, The NetherlandsElectron Microscopy Unit, Department of Pathology, Maastricht University, Maastricht, The NetherlandsDepartment of Neuroscience, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands, PO Box 616, 6200 MD Maastricht, The NetherlandsDepartment of Neuroscience, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands, PO Box 616, 6200 MD Maastricht, The Netherlands; Neuroimmunology Group, Biomedical Research Institute (BIOMED) Hasselt University, Diepenbeek, BelgiumDepartment of Neuroscience, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands, PO Box 616, 6200 MD Maastricht, The NetherlandsThe receptor-associated protein of the synapse (rapsyn) is required for anchoring and stabilizing the nicotinic acetylcholine receptor (AChR) in the postsynaptic membrane of the neuromuscular junction (NMJ) during development. Here we studied the role of rapsyn in the maintenance of the adult NMJ by reducing rapsyn expression levels with short hairpin RNA (shRNA). Silencing rapsyn led to the average reduction of the protein levels of rapsyn (31% loss) and AChR (36% loss) at the NMJ within 2 weeks, corresponding to previously reported half life of these proteins. On the other hand, the sodium channel protein expression was augmented (66%) in rapsyn-silenced muscles. Unexpectedly, at the ultrastructural level a significant increase in the amount of secondary folds of the postsynaptic membrane in silenced muscles was observed. The neuromuscular transmission in rapsyn-silenced muscles was mildly impaired. The results suggest that the adult NMJ can rapidly produce postsynaptic folds to compensate for AChR and rapsyn loss.http://www.sciencedirect.com/science/article/pii/S096999610900059XRapsynVoltage gated sodium channelMyasthenia gravisNeuromuscular junctionCongenital myasthenic syndromes |
| spellingShingle | Pilar Martínez-Martínez Marko Phernambucq Laura Steinbusch Laurent Schaeffer Sonia Berrih-Aknin Hans Duimel Peter Frederik Peter Molenaar Marc H. De Baets Mario Losen Silencing rapsyn in vivo decreases acetylcholine receptors and augments sodium channels and secondary postsynaptic membrane folding Neurobiology of Disease Rapsyn Voltage gated sodium channel Myasthenia gravis Neuromuscular junction Congenital myasthenic syndromes |
| title | Silencing rapsyn in vivo decreases acetylcholine receptors and augments sodium channels and secondary postsynaptic membrane folding |
| title_full | Silencing rapsyn in vivo decreases acetylcholine receptors and augments sodium channels and secondary postsynaptic membrane folding |
| title_fullStr | Silencing rapsyn in vivo decreases acetylcholine receptors and augments sodium channels and secondary postsynaptic membrane folding |
| title_full_unstemmed | Silencing rapsyn in vivo decreases acetylcholine receptors and augments sodium channels and secondary postsynaptic membrane folding |
| title_short | Silencing rapsyn in vivo decreases acetylcholine receptors and augments sodium channels and secondary postsynaptic membrane folding |
| title_sort | silencing rapsyn in vivo decreases acetylcholine receptors and augments sodium channels and secondary postsynaptic membrane folding |
| topic | Rapsyn Voltage gated sodium channel Myasthenia gravis Neuromuscular junction Congenital myasthenic syndromes |
| url | http://www.sciencedirect.com/science/article/pii/S096999610900059X |
| work_keys_str_mv | AT pilarmartinezmartinez silencingrapsyninvivodecreasesacetylcholinereceptorsandaugmentssodiumchannelsandsecondarypostsynapticmembranefolding AT markophernambucq silencingrapsyninvivodecreasesacetylcholinereceptorsandaugmentssodiumchannelsandsecondarypostsynapticmembranefolding AT laurasteinbusch silencingrapsyninvivodecreasesacetylcholinereceptorsandaugmentssodiumchannelsandsecondarypostsynapticmembranefolding AT laurentschaeffer silencingrapsyninvivodecreasesacetylcholinereceptorsandaugmentssodiumchannelsandsecondarypostsynapticmembranefolding AT soniaberrihaknin silencingrapsyninvivodecreasesacetylcholinereceptorsandaugmentssodiumchannelsandsecondarypostsynapticmembranefolding AT hansduimel silencingrapsyninvivodecreasesacetylcholinereceptorsandaugmentssodiumchannelsandsecondarypostsynapticmembranefolding AT peterfrederik silencingrapsyninvivodecreasesacetylcholinereceptorsandaugmentssodiumchannelsandsecondarypostsynapticmembranefolding AT petermolenaar silencingrapsyninvivodecreasesacetylcholinereceptorsandaugmentssodiumchannelsandsecondarypostsynapticmembranefolding AT marchdebaets silencingrapsyninvivodecreasesacetylcholinereceptorsandaugmentssodiumchannelsandsecondarypostsynapticmembranefolding AT mariolosen silencingrapsyninvivodecreasesacetylcholinereceptorsandaugmentssodiumchannelsandsecondarypostsynapticmembranefolding |