Silencing rapsyn in vivo decreases acetylcholine receptors and augments sodium channels and secondary postsynaptic membrane folding

NEUROBIOLOGY OF DISEASE

卷:35

Article

Martinez-Martinez, Pilar¹  Phemambucq, Marko¹  Steinbusch, Laura¹  Schaeffer, Laurent²  Berrih-Aknin, Sonia³  Duimel, Hans⁴  Frederik, Peter⁴  Molenaar, Peter¹  De Baets, Marc H.^1,5  Losen, Mario¹ 

[1] Maastricht Univ, Dept Neurosci, Sch Mental Hlth & Neurosci, NL-6200 MD Maastricht, Netherlands

[2] Ecole Normale Super Lyon, Equipe Differenciat Neuromusculaire, Inst Federatif Rech 128, Ctr Natl Rech Sci,Unite Mixte Rech 5161, F-69364 Lyon 07, France

[3] Univ Paris 11, Hop Marie Lannelongue, CNRS, IPSC,UMR 8162, Paris, France

[4] Maastricht Univ, Dept Pathol, Electron Microscopy Unit, NL-6200 MD Maastricht, Netherlands

[5] Hasselt Univ, Biomed Res Inst BIOMED, Neuroimmunol Grp, Diepenbeek, Belgium

关键词: Rapsyn;    Voltage gated sodium channel;    Myasthenia gravis;    Neuromuscular junction;    Congenital myasthenic syndromes;   

DOI  :  10.1016/j.nbd.2009.03.008

来源: Elsevier

【 摘 要 】

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. (C) 2009 Elsevier Inc. All rights reserved.

【 授权许可】

Free