Sarcoglycan Alpha Mitigates Neuromuscular Junction Decline in Aged Mice by Stabilizing LRP4

doi:10.1523/JNEUROSCI.0860-18.2018

	Sarcoglycan Alpha Mitigates Neuromuscular Junction Decline in Aged Mice by Stabilizing LRP4
	Zhao, Kai 1,3; Shen, Chengyong 3,4; Li, Lei1,3,5 ; Wu, Haitao 3,6; Xing, Guanglin 1; Dong, Zhaoqi 1; Jing, Hongyang 1; Chen, Wenbing 1; Zhang, Hongsheng 1; Tan, Zhibing 1; Pan, Jinxiu 1; Xiong, Lei 1; Wang, Hongsheng 1; Cui, Wanpeng 1; Sun, Xiang-Dong 3,7; Li, Shihua 8; Huang, Xinping 9; Xiong, Wen-Cheng 1,2,3; Mei, Lin 1,2,3
	2018-10-10
发表期刊	JOURNAL OF NEUROSCIENCE (IF:4.4[JCR-2023],5.3[5-Year])
ISSN	0270-6474
卷号	38 期号:41 页码:8860-8873
发表状态	已发表
DOI	10.1523/JNEUROSCI.0860-18.2018
摘要	During aging, acetylcholine receptor (AChR) clusters become fragmented and denervated at the neuromuscular junction (NMJ). Under-pinning molecular mechanisms are not well understood. We showed that LRP4, a receptor for agrin and critical for NMJ formation and maintenance, was reduced at protein level in aged mice, which was associated with decreased MuSK tyrosine phosphorylat ion, suggesting compromised agrin-LRP4-MuSK signaling in aged muscles. Transgenic expression of LRP4 in muscles alleviated AChR fragmentation and denervation and improved neuromuscular transmission in aged mice. LRP4 ubiquitination was augmented in aged muscles, suggesting increased LRP4 degradation as a mechanism for reduced LRP4. We found that sarcoglycan alpha (SG alpha) interacted with LRP4 and delayed LRP4 degradation in cotransfected cells. AAV9-mediated expression of SG alpha in muscles mitigated AChR fragmentation and denervation and improved neuromuscular transmission in aged mice. These observations support a model where compromised agrinLRP4-MuSK signaling serves as a pathological mechanism of age-related NMJ decline and identify a novel function of SG alpha in stabilizing LRP4 for NMJ stability in aged mice.
关键词	aging LRP4 neuromuscular junction SG alpha
收录类别	SCI ; SCIE
语种	英语
资助项目	Viral Vector core at Emory University Department of Neurology (NINDS Core Facilities Grant)[P30NS055077]
WOS研究方向	Neurosciences & Neurology
WOS类目	Neurosciences
WOS记录号	WOS:000446842200012
出版者	SOC NEUROSCIENCE
WOS关键词	DYSTROPHIN-GLYCOPROTEIN COMPLEX ; DUCHENNE MUSCULAR-DYSTROPHY ; SKELETAL-MUSCLE FIBERS ; TYROSINE KINASE MUSK ; MYASTHENIA-GRAVIS ; MOTOR UNIT ; AGRIN RECEPTOR ; DEFICIENT MICE ; RAT MUSCLE ; END-PLATES
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/28084
专题	生命科学与技术学院生命科学与技术学院_PI研究组_李磊组
通讯作者	Shen, Chengyong; Mei, Lin
作者单位	1.Case Western Reserve Univ, Sch Med, Dept Neurosci, 10900 Euclid Ave, Cleveland, OH 44106 USA 2.Louis Stokes Cleveland Vet Affairs Med Ctr, Cleveland, OH 44106 USA 3.Augusta Univ, Med Coll Georgia, Dept Neurosci & Regenerat Med, Augusta, GA 30912 USA 4.Zhejiang Univ, Affiliated Hosp 1, Inst Translat Med, 268 Kaixuan Rd, Hangzhou 310020, Zhejiang, Peoples R China 5.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 6.Inst Basic Med Sci, Dept Neurobiol, Beijing 100850, Peoples R China 7.Guangzhou Med Univ, Affiliated Hosp 2, Sch Basic Med Sci, Dept Neurol, Guangzhou 510260, Guangdong, Peoples R China 8.Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA 9.Emory Univ, Ctr Neurodegenerat Dis, Sch Med, Atlanta, GA 30322 USA
推荐引用方式 GB/T 7714	Zhao, Kai,Shen, Chengyong,Li, Lei,et al. Sarcoglycan Alpha Mitigates Neuromuscular Junction Decline in Aged Mice by Stabilizing LRP4[J]. JOURNAL OF NEUROSCIENCE,2018,38(41):8860-8873.
APA	Zhao, Kai.,Shen, Chengyong.,Li, Lei.,Wu, Haitao.,Xing, Guanglin.,...&Mei, Lin.(2018).Sarcoglycan Alpha Mitigates Neuromuscular Junction Decline in Aged Mice by Stabilizing LRP4.JOURNAL OF NEUROSCIENCE,38(41),8860-8873.
MLA	Zhao, Kai,et al."Sarcoglycan Alpha Mitigates Neuromuscular Junction Decline in Aged Mice by Stabilizing LRP4".JOURNAL OF NEUROSCIENCE 38.41(2018):8860-8873.