Role of protein kinase C in the induction and maintenance of serotonin-dependent enhancement of the glutamate response in isolated siphon motor neurons of Aplysia californica.
Role of protein kinase C in the induction and maintenance of serotonin-dependent enhancement of the glutamate response in isolated siphon motor neurons of Aplysia californica.
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DOI：
10.1523/jneurosci.4149-08.2009
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发表时间：
2009-04-22
期刊：
影响因子：
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通讯作者：
Glanzman DL
中科院分区：
文献类型：
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作者：
Villareal G;Li Q;Cai D;Fink AE;Lim T;Bougie JK;Sossin WS;Glanzman DL
5-羟色胺（5-HT）介导的学习相关的易化的感觉运动突触在失语症。在某些情况下，5-HT依赖性易化需要蛋白激酶C（PKC）的活性。PKC参与5-HT依赖性突触易化的一个关键部位是突触前感觉神经元。在这里，我们提供的证据表明，突触后PKC也有助于突触易化。我们研究了PKC对细胞培养的虹吸运动神经元谷氨酸诱发电位（Glu-EP）增强的作用。应用5-HT或佛波酯（激活PKC）10分钟，产生持续（> 50分钟）的Glu-EP增强。白屈菜红碱和双吲哚马来酰亚胺-1（Bis），两种PKC抑制剂，都阻断了5-HT依赖性增强的诱导。钙蛋白酶（一种钙依赖性蛋白酶）的抑制剂也阻断了5-HT的作用。有趣的是，白屈菜红碱阻断了增强的维持，而Bis没有。由于Bis对PKC的常规和新型异构体比非典型异构体具有更大的选择性，因此该结果暗示非典型异构体在维持5-HT的作用中。虽然诱导增强的谷氨酸-EP需要蛋白质的合成，我们发现，维护的增强不。5-HT依赖性增强的维持似乎是由非典型PKC的钙蛋白酶依赖性蛋白水解产生的PKM型片段介导的。两者合计，我们的研究结果表明，5-HT治疗触发两个阶段的运动神经元内的PKC活性，早期阶段，可能涉及传统的，新的或非典型的PKC亚型，和后期阶段，选择性地涉及一个非典型的亚型。
Serotonin (5-HT) mediates learning-related facilitation of sensorimotor synapses in Aplysia. Under some circumstances 5-HT-dependent facilitation requires the activity of protein kinase C (PKC). One critical site of PKC’s contribution to 5-HT-dependent synaptic facilitation is the presynaptic sensory neuron. Here, we provide evidence that postsynaptic PKC also contributes to synaptic facilitation. We investigated the contribution of PKC to enhancement of the glutamate-evoked potential (Glu-EP) in isolated siphon motor neurons in cell culture. A 10-min application of either 5-HT or phorbol ester, which activates PKC, produced persistent (> 50 min) enhancement of the Glu-EP. Chelerythrine and bisindolylmaleimide-1 (Bis), two inhibitors of PKC, both blocked the induction of 5-HT-dependent enhancement. An inhibitor of calpain, a calcium-dependent protease, also blocked 5-HT’s effect. Interestingly, whereas chelerythrine blocked maintenance of the enhancement, Bis did not. Because Bis has greater selectivity for conventional and novel isoforms of PKC than for atypical isoforms, this result implicates an atypical isoform in the maintenance of 5-HT’s effect. Although induction of enhancement of the Glu-EP requires protein synthesis, we found that maintenance of the enhancement does not. Maintenance of 5-HT-dependent enhancement appears to be mediated by a PKM-type fragment generated by calpain-dependent proteolysis of atypical PKC. Taken together, our results suggest that 5-HT treatment triggers two phases of PKC activity within the motor neuron, an early phase that may involve conventional, novel or atypical isoforms of PKC, and a later phase that selectively involves an atypical isoform.