The Temporal Pattern of Stimulation Determines the Extent and Duration of MAPK Activation in a Caenorhabditis elegans Sensory Neuron
The Temporal Pattern of Stimulation Determines the Extent and Duration of MAPK Activation in a Caenorhabditis elegans Sensory Neuron
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DOI：
10.1126/scisignal.2002983
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发表时间：
2012-10-16
影响因子：
7.3
通讯作者：
Saito, Haruo
中科院分区：
文献类型：
--
作者：
Tomida, Taichiro;Oda, Shigekazu;Saito, Haruo
环境NaCl浓度降低时，秀丽隐杆线虫ASER感觉神经元兴奋。丝裂原活化蛋白激酶（MAPK）MPK-1是ERK（细胞外信号调节激酶）的同源物，在ASER感觉神经元兴奋期间被激活。我们在ASER神经元中创建并表达了基于荧光共振能量转移（FRET）的MAPK活性探针，然后将蠕虫暴露于各种循环模式的刺激（NaCl浓度的变化）以监测MPK-1活性的动态。我们发现MPK-1活性的强度和持续时间由刺激的时间模式决定，即刺激周期长度、刺激持续时间和刺激之间的时间的组合。刺激和MPK-1激活之间的复杂的非线性关系可以通过MPK-1上游的细胞内钙反应的性质来解释。因此，我们可视化的动态MAPK激活的感觉神经元在活的线虫在复杂的刺激，并提出了一个报告，可用于高等真核生物中的MAPK通路的计算机预测测试。
The Caenorhabditis elegans ASER sensory neuron is excited when environmental NaCl concentration is decreased. The mitogen-activated protein kinase (MAPK) MPK-1, a homolog of ERK (extracellular signal-regulated kinase), is activated during excitation of ASER sensory neurons. We created and expressed a fluorescence resonance energy transfer (FRET)-based MAPK activity probe in ASER neurons and then exposed the worms to various cyclic patterns of stimulation (changes in NaCl concentration) to monitor the dynamics of MPK-1 activity. We found that the intensity and duration of MPK-1 activity were determined by the temporal pattern of stimulation, namely, a combination of stimulation period length, stimulation duration, and time between stimuli. The complex, nonlinear relationship between stimulation and MPK-1 activation was explained by the properties of intracellular calcium responses upstream of MPK-1. Thus, we visualized the dynamics of MAPK activation in a sensory neuron in living nematodes in response to complex stimuli and present a reporter that can be used in higher eukaryotes to test in silico predictions regarding the MAPK pathway.