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Title: Muscle-specific receptor tyrosine kinase endocytosis in acetylcholine receptor clustering in response to agrin
Author: Zhu, Dan ; Yang, Zhihua ; Luo, Zhenge ; Luo, Shiwen ; Xiong, Wen C. ; Mei, Lin
Source: JOURNAL OF NEUROSCIENCE
Issued Date: 2008
Volume: 28, Issue:7, Pages:1688-1696
Keyword: neuromuscular junction ; nicotinic acetylcholine receptors ; agrin ; endocytosis ; MuSK ; NSF ; JUNCTION IN-VIVO ; SENSITIVE FUSION PROTEIN ; NEUROMUSCULAR-JUNCTION ; SIGNAL-TRANSDUCTION ; MEDIATED ENDOCYTOSIS ; TRANSPORT VESICLES ; PLASMA-MEMBRANE ; CLATHRIN ; MUSK ; CAVEOLAE
Subject: Neurosciences & Neurology
Corresponding Author: Mei, L (reprint author), Med Coll Georgia, Inst Mol Med & Genet, Program Dev Neurobiol, 1120 15th St, Augusta, GA 30912 USA,lmei@mcg.edu
English Abstract: Agrin, a factor used by motoneurons to direct acetylcholine receptor (AChR) clustering at the neuromuscular junction, initiates signal transduction by activating the muscle-specific receptor tyrosine kinase (MuSK). However, the underlying mechanisms remain poorly defined. Here, we demonstrated that MuSK became rapidly internalized in response to agrin, which appeared to be required for induced AChR clustering. Moreover, we provided evidence for a role of N-ethylmaleimide sensitive factor (NSF) in regulating MuSK endocytosis and subsequent signaling in response to agrin stimulation. NSF interacts directly with MuSK with nanomolar affinity, and treatment of muscle cells with the NSF inhibitor N-ethylmaleimide, mutation of NSF, or suppression of NSF expression all inhibited agrin-induced AChR clustering. Furthermore, suppression of NSF expression and NSF mutation attenuate MuSK downstream signaling. Our study reveals a potentially novel mechanism that regulates agrin/MuSK signaling cascade.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1738
Appears in Collections:神经所(总)_期刊论文

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Zhu, Dan; Yang, Zhihua; Luo, Zhenge; Luo, Shiwen; Xiong, Wen C.; Mei, Lin.Muscle-specific receptor tyrosine kinase endocytosis in acetylcholine receptor clustering in response to agrin,JOURNAL OF NEUROSCIENCE,2008,28(7):1688-1696
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