Global analysis of neuronal phosphoproteome regulation by chondroitin sulfate proteoglycans.
Global analysis of neuronal phosphoproteome regulation by chondroitin sulfate proteoglycans.
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DOI：
10.1371/journal.pone.0059285
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Geller HM
中科院分区：
文献类型：
--
作者：
Yu P;Pisitkun T;Wang G;Wang R;Katagiri Y;Gucek M;Knepper MA;Geller HM
硫酸软骨素蛋白聚糖（CSPGs）是介导中枢神经系统损伤后轴突再生抑制的细胞外基质的主要成分。最近已经确定了几种CSPGs的神经元受体；然而，CSPGs限制轴突生长的信号通路在很大程度上仍然未知。在本研究中，我们应用定量磷酸化蛋白质组学研究了CSPGs在原代神经元中诱导的蛋白磷酸化的整体变化。结合iTRAQ标记、强阳离子交换色谱（SCX）分离、固定化金属亲和色谱（IMAC）和LC-MS/MS，我们鉴定并定量了1118个磷酸化蛋白对应的2214个独特的磷酸肽，其中118个在CSPG处理下丰度发生了显著变化。受CSPGs调控的蛋白包括突触囊泡运输的关键组分、信号素介导的轴突引导、整合素信号传导、钙粘蛋白信号传导和EGF受体信号传导途径。大量受调节的蛋白质是细胞骨架蛋白和相关蛋白，它们与调节神经突生长有关。另一个受CSPGs调控的高度代表性的蛋白质类别是参与RNA转录后调控的核酸结合蛋白。总之，通过筛选CSPG诱导的整体磷蛋白组变化，该数据扩展了我们对CSPG信号传导的理解，为克服CSPG抑制和促进CNS损伤后轴突再生的策略开发提供了新的见解。
Chondroitin sulfate proteoglycans (CSPGs) are major components of the extracellular matrix which mediate inhibition of axonal regeneration after injury to the central nervous system (CNS). Several neuronal receptors for CSPGs have recently been identified; however, the signaling pathways by which CSPGs restrict axonal growth are still largely unknown. In this study, we applied quantitative phosphoproteomics to investigate the global changes in protein phosphorylation induced by CSPGs in primary neurons. In combination with isobaric Tags for Relative and Absolute Quantitation (iTRAQ) labeling, strong cation exchange chromatography (SCX) fractionation, immobilized metal affinity chromatography (IMAC) and LC-MS/MS, we identified and quantified 2214 unique phosphopeptides corresponding to 1118 phosphoproteins, with 118 changing significantly in abundance with CSPG treatment. The proteins that were regulated by CSPGs included key components of synaptic vesicle trafficking, axon guidance mediated by semaphorins, integrin signaling, cadherin signaling and EGF receptor signaling pathways. A significant number of the regulated proteins are cytoskeletal and related proteins that have been implicated in regulating neurite growth. Another highly represented protein category regulated by CSPGs is nucleic acid binding proteins involved in RNA post-transcriptional regulation. Together, by screening the overall phosphoproteome changes induced by CSPGs, this data expand our understanding of CSPG signaling, which provides new insights into development of strategies for overcoming CSPG inhibition and promoting axonal regeneration after CNS injury.
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影响因子：
7.8
作者：
BALSAMO, J;ERNST, H;ZANIN, MKB;HOFFMAN, S;LILIEN, J
通讯作者：
LILIEN, J
影响因子：
7
作者：
Ross, PL;Huang, YLN;Pappin, DJ
通讯作者：
Pappin, DJ
影响因子：
4.8
作者：
Hlavanda, Emma;Klement, Eva;Ovadi, Judit
通讯作者：
Ovadi, Judit
影响因子：
5.3
作者：
Fu, Qiao;Hue, Jeongsim;Li, Shuxin
通讯作者：
Li, Shuxin
影响因子：
7
作者：
Hoffert, Jason D.;Pisitkun, Trairak;Knepper, Mark A.
通讯作者：
Knepper, Mark A.