摘要: The receptor tyrosine kinase MuSK (muscle-specific kinase) is the key signaling molecule during formation of a mature and functional neuromuscular junction (NMJ). Signal transduction events downstream activation induce both pre- postsynaptic differentiation, which, most prominently, includes clustering acetylcholine receptors (AChRs) at synaptic sites. requires complex interplay between its co-receptor Lrp4 (low-density lipoprotein receptor-related protein-4), motor neuron-derived heparan-sulfate proteoglycan Agrin intracellular adaptor protein Dok-7. A tight regulation activity crucial for proper NMJ development. Defects in are cause muscle weakness as reported congenital myasthenic syndromes myasthenia gravis. This review focuses on recent structure-based analyses MuSK, Agrin, Dok-7 interactions their function activation. Conclusions about that were derived from molecular structures will be highlighted. In addition, role development disease discussed.
sci-hub.se 参考文章(120)
Weichun Lin, Robert W. Burgess, Bertha Dominguez, Samuel L. Pfaff, Joshua R. Sanes, Kuo-Fen Lee, Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse Nature. ,vol. 410, pp. 1057- 1064 ,(2001) , 10.1038/35074025
Jeffrey H. Till, Manuel Becerra, Anke Watty, Yun Lu, Yuliang Ma, Thomas A. Neubert, Steven J. Burden, Stevan R. Hubbard, Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation. Structure. ,vol. 10, pp. 1187- 1196 ,(2002) , 10.1016/S0969-2126(02)00814-6
Werner Hoch, John McConville, Sigrun Helms, John Newsom-Davis, Arthur Melms, Angela Vincent, Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies Nature Medicine. ,vol. 7, pp. 365- 368 ,(2001) , 10.1038/85520
Joshua R. Sanes, Jeff W. Lichtman, Induction, assembly, maturation and maintenance of a postsynaptic apparatus Nature Reviews Neuroscience. ,vol. 2, pp. 791- 805 ,(2001) , 10.1038/35097557
Norihiro Yumoto, Natalie Kim, Steven J. Burden, Lrp4 is a retrograde signal for presynaptic differentiation at neuromuscular synapses Nature. ,vol. 489, pp. 438- 442 ,(2012) , 10.1038/NATURE11348
Alexander Sorkin, Mark von Zastrow, Endocytosis and signalling: intertwining molecular networks Nature Reviews Molecular Cell Biology. ,vol. 10, pp. 609- 622 ,(2009) , 10.1038/NRM2748
Xian Chu Kong, Patrizia Barzaghi, Markus A Ruegg, Inhibition of synapse assembly in mammalian muscle in vivo by RNA interference EMBO Reports. ,vol. 5, pp. 183- 188 ,(2004) , 10.1038/SJ.EMBOR.7400065
Viktoria Nizhynska, Ralph Neumueller, Ruth Herbst, Phosphoinositide 3-kinase acts through RAC and Cdc42 during agrin-induced acetylcholine receptor clustering. Developmental Neurobiology. ,vol. 67, pp. 1047- 1058 ,(2007) , 10.1002/DNEU.20371
Boris A. Hesser, Oliver Henschel, Veit Witzemann, Synapse disassembly and formation of new synapses in postnatal muscle upon conditional inactivation of MuSK. Molecular and Cellular Neuroscience. ,vol. 31, pp. 470- 480 ,(2006) , 10.1016/J.MCN.2005.10.020
H. Wu, W. C. Xiong, L. Mei, To build a synapse: Signaling pathways in neuromuscular junction assembly Development. ,vol. 137, pp. 1017- 1033 ,(2010) , 10.1242/DEV.038711