Profiling synaptic proteins identifies regulators of insulin secretion and lifespan.
Profiling synaptic proteins identifies regulators of insulin secretion and lifespan.
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分析突触蛋白鉴定了胰岛素分泌和寿命的调节剂。
DOI：
10.1371/journal.pgen.1000283
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发表时间：
2008-11
期刊：
影响因子：
4.5
通讯作者：
Kaplan, Joshua M.
中科院分区：
文献类型：
--
作者：
Ch'ng, QueeLim;Sieburth, Derek;Kaplan, Joshua M.
细胞被组织成不同的隔间，以空间精度执行特定的任务。在神经元中，突触前特化是专门用于神经递质分泌的生化复杂的亚细胞结构。突触前蛋白质丰度的活动依赖性变化被认为赋予突触不同的功能状态;然而，对突触前末梢组成变化的规则知之甚少。我们描述了一种遗传策略，系统地分析蛋白质定位在秀丽隐杆线虫突触前专业化。九突触前蛋白GFP标记，允许多个突触前结构的可视化。这些蛋白质的分布和丰度的变化在25个突变体中进行了定量，这些突变体改变了神经传递的不同方面。对这些数据的全局分析确定了特定突触前组分之间的新关系，并提供了一种通过识别共享蛋白定位表型来比较基因功能的新方法。使用这种策略，我们确定了几个基因，调节胰岛素样生长因子（IGF）的分泌，并影响寿命的方式依赖于胰岛素/IGF信号。细胞被分成多个亚细胞区室，执行不同的功能。在神经元中，突触介导细胞之间的信息传递，它们包含数百种专用于此目的的蛋白质。突触的蛋白质组成的变化被认为会引起突触传递的变化，例如在发育，学习和记忆过程中发生的变化。在这里，我们描述了一个系统的遗传策略，用于分析突触的蛋白质组成。使用这种策略，我们确定了以类似方式改变突触的基因组，并确定了特定突触蛋白之间的新型调控关系。一组基因调节神经元分泌胰岛素样激素，并对寿命产生相应的影响，这是由胰岛素信号控制的。这些结果说明了如何在突触组成的变化可以被用作探针来解释生理变化。我们的方法可以扩展到包括一个更大的突触蛋白或分析其他亚细胞区室。
Cells are organized into distinct compartments to perform specific tasks with spatial precision. In neurons, presynaptic specializations are biochemically complex subcellular structures dedicated to neurotransmitter secretion. Activity-dependent changes in the abundance of presynaptic proteins are thought to endow synapses with different functional states; however, relatively little is known about the rules that govern changes in the composition of presynaptic terminals. We describe a genetic strategy to systematically analyze protein localization at Caenorhabditis elegans presynaptic specializations. Nine presynaptic proteins were GFP-tagged, allowing visualization of multiple presynaptic structures. Changes in the distribution and abundance of these proteins were quantified in 25 mutants that alter different aspects of neurotransmission. Global analysis of these data identified novel relationships between particular presynaptic components and provides a new method to compare gene functions by identifying shared protein localization phenotypes. Using this strategy, we identified several genes that regulate secretion of insulin-like growth factors (IGFs) and influence lifespan in a manner dependent on insulin/IGF signaling. Cells are divided into multiple subcellular compartments that perform diverse functions. In neurons, synapses mediate transmission of information between cells and they comprise hundreds of proteins dedicated for this purpose. Changes in the protein composition of synapses are thought to produce changes in synaptic transmission, such as those that occur during development, learning, and memory. Here, we describe a systematic genetic strategy for analyzing the protein composition of synapses. Using this strategy, we identified sets of genes that alter synapses in similar ways, and identified novel regulatory relationships between particular synaptic proteins. One set of genes regulated secretion of insulin-like hormones from neurons and had corresponding effects on lifespan, which is controlled by insulin signaling. These results illustrate how changes in synaptic composition can be utilized as a probe to explain changes in physiology. Our approach can be expanded to include a larger set of synaptic proteins or to analyze other subcellular compartments.
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影响因子：
2.5
作者：
Gracheva EO;Hadwiger G;Nonet ML;Richmond JE
通讯作者：
Richmond JE
DOI：
10.1083/jcb.150.3.589
发表时间：
2000-08-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
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影响因子：
16.2
作者：
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通讯作者：
Simon, MI
影响因子：
16.2
作者：
Crump, JG;Zhen, M;Bargmann, CI
通讯作者：
Bargmann, CI
影响因子：
10.5
作者：
Hamilton, B;Doug, YQ;Lee, SS
通讯作者：
Lee, SS