Silencing rapsyn in vivo decreases acetylcholine receptors and augments sodium channels and secondary postsynaptic membrane folding.
作者： Pilar Martínez-Martínez , Marko Phernambucq , Laura Steinbusch , Laurent Schaeffer , Sonia Berrih-Aknin
DOI: 10.1016/J.NBD.2009.03.008
关键词:
摘要: The receptor-associated protein of the synapse (rapsyn) is required for anchoring and stabilizing nicotinic acetylcholine receptor (AChR) in postsynaptic membrane neuromuscular junction (NMJ) during development. Here we studied role rapsyn maintenance adult NMJ by reducing expression levels with short hairpin RNA (shRNA). Silencing led to average reduction (31% loss) AChR (36% at within 2 weeks, corresponding previously reported half life these proteins. On other hand, sodium channel was augmented (66%) rapsyn-silenced muscles. Unexpectedly, ultrastructural level a significant increase amount secondary folds silenced muscles observed. transmission mildly impaired. results suggest that can rapidly produce compensate loss.
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Angela Reynolds, Emily M Anderson, Annaleen Vermeulen, Yuriy Fedorov, Kathryn Robinson, Devin Leake, Jon Karpilow, William S Marshall, Anastasia Khvorova, Induction of the interferon response by siRNA is cell type- and duplex length-dependent. RNA. ,vol. 12, pp. 988- 993 ,(2006) , 10.1261/RNA.2340906
Kinji Ohno, Menachem Sadeh, Ilan Blatt, Joan M Brengman, Andrew G Engel, E-box mutations in the RAPSN promoter region in eight cases with congenital myasthenic syndrome Human Molecular Genetics. ,vol. 12, pp. 739- 748 ,(2003) , 10.1093/HMG/DDG089
T. Tuschl, P. D. Zamore, R. Lehmann, D. P. Bartel, P. A. Sharp, Targeted mRNA degradation by double-stranded RNA in vitro Genes & Development. ,vol. 13, pp. 3191- 3197 ,(1999) , 10.1101/GAD.13.24.3191
Thomas M DeChiara, David C Bowen, David M Valenzuela, Mary V Simmons, William T Poueymirou, Susan Thomas, Erika Kinetz, Debra L Compton, Eduardo Rojas, John S Park, Cynthia Smith, Peter S DiStefano, David J Glass, Steven J Burden, George D Yancopoulos, The Receptor Tyrosine Kinase MuSK Is Required for Neuromuscular Junction Formation In Vivo Cell. ,vol. 85, pp. 501- 512 ,(1996) , 10.1016/S0092-8674(00)81251-9
R M Nitkin, M A Smith, C Magill, J R Fallon, Y M Yao, B G Wallace, U J McMahan, Identification of agrin, a synaptic organizing protein from Torpedo electric organ. Journal of Cell Biology. ,vol. 105, pp. 2471- 2478 ,(1987) , 10.1083/JCB.105.6.2471
T. Misgeld, T. T. Kummer, J. W. Lichtman, J. R. Sanes, Agrin promotes synaptic differentiation by counteracting an inhibitory effect of neurotransmitter. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 102, pp. 11088- 11093 ,(2005) , 10.1073/PNAS.0504806102
Kinji Ohno, Andrew G. Engel, Xin-Ming Shen, Duygu Selcen, Joan Brengman, C. Michel Harper, Akira Tsujino, Margherita Milone, Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome. American Journal of Human Genetics. ,vol. 70, pp. 875- 885 ,(2002) , 10.1086/339465
Mario Losen, Maurice H. W. Stassen, Pilar Martínez-Martínez, Barbie M. Machiels, Hans Duimel, Peter Frederik, Henk Veldman, John H. J. Wokke, Frank Spaans, Angela Vincent, Marc H. De Baets, Increased expression of rapsyn in muscles prevents acetylcholine receptor loss in experimental autoimmune myasthenia gravis Brain. ,vol. 128, pp. 2327- 2337 ,(2005) , 10.1093/BRAIN/AWH612
Jun Kimura, Electrodiagnosis in Diseases of Nerve and Muscle: Principles and Practice ,(1983)
Kirk Brown, Dmitry Samarsky, RNAi off-targeting: Light at the end of the tunnel. Journal of RNAi and gene silencing : an international journal of RNA and gene targeting research. ,vol. 4, pp. 175- 177 ,(2006)