Identification of ciliary neurotrophic factor receptor alpha as a mediator of neurotoxicity induced by alpha-synuclein.
Identification of ciliary neurotrophic factor receptor alpha as a mediator of neurotoxicity induced by alpha-synuclein.
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DOI：
10.1002/pmic.200900745
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发表时间：
2010-06
期刊：
影响因子：
3.4
通讯作者：
Zhang, Jing
中科院分区：
文献类型：
--
作者：
Liu, Jun;Shi, Min;Hong, Zhen;Zhang, JianPeng;Bradner, Joshua;Quinn, Thomas;Beyer, Richard P.;Mcgeer, Patrick L.;Chen, ShengDi;Zhang, Jing
越来越多的证据表明，细胞外α-突触核蛋白(ESNCA)通过小胶质细胞或星形胶质细胞的激活直接或间接地诱导神经毒性，在帕金森病(PD)或相关的突触核病的发病机制中发挥重要作用。然而，发生这种情况的机制仍有待描述。为了探索这些机制，我们结合了三种生化技术-细胞培养中氨基酸的稳定同位素标记(SILAC)；质膜蛋白的生物素标记然后亲和纯化；以及在膜阵列上分析与SNCA肽结合的独特蛋白质。SILAC蛋白质组分析确定了457个蛋白质，其中245个或172个蛋白质属于膜或膜相关蛋白质，这取决于用于解释的各种生物信息学工具。与未处理细胞相比，eSNCA处理的多巴胺神经元细胞中86种膜蛋白表达水平升高，35种膜蛋白表达水平降低。在多肽阵列分析中，鉴定出127个蛋白可能与eSNCA相互作用。其中有7个蛋白与eSNCA处理后相对丰度发生变化的膜蛋白重叠。一种是睫状神经营养因子受体α(CNTFR-α)，它似乎通过与JAK1/STAT3信号相关但不依赖eSNCA内吞作用的机制来调节eSNCA介导的神经毒性。
Accumulating evidence suggests that extracellular α-synuclein (eSNCA) plays an important role in the pathogenesis of Parkinson's disease (PD) or related synucleinopathies by inducing neurotoxicity directly or indirectly via microglial or astroglial activation. However, the mechanisms by which this occurs remain to be characterized. To explore these mechanisms, we combined three biochemical techniques - Stable Isotope Labeling of Amino acid in Cell cultures (SILAC); biotin labeling of plasma membrane proteins followed by affinity purification; and analysis of unique proteins binding to SNCA peptides on membrane arrays. The SILAC proteomic analysis identified 457 proteins, of which, 245 or 172 proteins belonged to membrane or membrane associated proteins, depending on the various bioinformatics tools used for interpretation. In dopamine neuronal cells treated with eSNCA, the levels of 86 membrane proteins were increased and 35 were decreased compared with untreated cells. In peptide array analysis, 127 proteins were identified as possibly interacting with eSNCA. Of those, seven proteins were overlapped with the membrane proteins that displayed alterations in relative abundance after eSNCA treatment. One was ciliary neurotrophic factor receptor alpha (CNTFR-α), which appeared to modulate eSNCA-mediated neurotoxicity via mechanisms related to JAK1/STAT3 signaling but independent of eSNCA endocytosis.
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DOI：
10.1523/jneurosci.6202-08.2009
发表时间：
2009-02-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Liu J;Zhang JP;Shi M;Quinn T;Bradner J;Beyer R;Chen S;Zhang J
通讯作者：
Zhang J
影响因子：
11
作者：
Chiba, T.;Yamada, M.;Aiso, S.
通讯作者：
Aiso, S.
影响因子：
56.9
作者：
DAVIS, S;ALDRICH, TH;YANCOPOULOS, GD
通讯作者：
YANCOPOULOS, GD
影响因子：
7
作者：
Nunomura, K;Nagano, K;Isobe, T
通讯作者：
Isobe, T
影响因子：
3.1
作者：
Lee, Seung-Jae
通讯作者：
Lee, Seung-Jae