Identification of the key amino acids of glial cell line-derived neurotrophic factor family receptor alpha 1 involved in its biological function

	Identification of the key amino acids of glial cell line-derived neurotrophic factor family receptor alpha 1 involved in its biological function
	Wang, LM; Zhang, Q; Zhang, Q; Zhu, W; He, C; Lu, CL; Ding, DF; Chen, ZY
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2004
卷号	279 期号:1 页码:109-116
通讯作者	Ding, DF (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Proteom, 320 Yue Yang Rd Shanghai, Shanghai 200031, Peoples R China.,dingdafu@server.shcnc.ac.cn ; zheyu_chen@hotmail.com
英文摘要	Glial cell line-derived neurotrophic factor (GDNF) plays a critical role in neurodevelopment and survival of midbrain dopaminergic and spinal motor neurons in vitro and in vivo. The biological actions of GDNF are mediated by a two-receptor complex consisting of a glycosylphosphatidylinositol-linked cell surface molecule, the GDNF family receptor alpha1 (GFRalpha1), and receptor protein tyrosine kinase Ret. Although structural analysis of GDNF has been extensively examined, less is known about the structural basis of GFRalpha1 function. In this study, based on evolutionary trace method and relative solvent accessibility prediction of residues, a set of trace residues that are solvent-accessible was selected for site-directed mutagenesis. A series of GFRalpha1 mutations was made, and PC12 cell lines stably expressing different GFRalpha1 mutants were generated. According to the survival and differentiation responses of these stable PC12 cells upon GDNF stimulation and the GDNF-GFRalpha1-Ret interaction assay, residues (NN153)-N-152, Arg(259), and (SNS318)-S-316 in the GFRalpha1 central region were found to be critical for GFRalpha1 binding to GDNF and eliciting downstream signal transduction. The single mutation R259A in the GFRalpha1 molecule simultaneously lost its binding ability to GDNF and Ret. However N152A/N153A or S316A/N317A/S318A mutation in the GFRalpha1 molecule still retained the ability to bind with Ret. These findings suggest that distinct structural elements in GFRalpha1 may be involved in binding to GDNF and Ret.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	MIDBRAIN DOPAMINERGIC-NEURONS ; TYROSINE KINASE ; RET RECEPTOR ; GDNF ; BINDING ; PROTEIN ; NEURTURIN ; SURVIVAL ; COMPLEX ; DIFFERENTIATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000187555300014
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2022]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Wang, LM,Zhang, Q,Zhang, Q,et al. Identification of the key amino acids of glial cell line-derived neurotrophic factor family receptor alpha 1 involved in its biological function[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2004,279(1):109-116.
APA	Wang, LM.,Zhang, Q.,Zhang, Q.,Zhu, W.,He, C.,...&Chen, ZY.(2004).Identification of the key amino acids of glial cell line-derived neurotrophic factor family receptor alpha 1 involved in its biological function.JOURNAL OF BIOLOGICAL CHEMISTRY,279(1),109-116.
MLA	Wang, LM,et al."Identification of the key amino acids of glial cell line-derived neurotrophic factor family receptor alpha 1 involved in its biological function".JOURNAL OF BIOLOGICAL CHEMISTRY 279.1(2004):109-116.