The balance between postsynaptic Ca2+-dependent protein kinase and phosphatase activities controlling synaptic strength
The balance between postsynaptic Ca2+-dependent protein kinase and phosphatase activities controlling synaptic strength
复制标题
DOI：
10.1101/lm.3.2-3.170
复制
发表时间：
1996-09-01
影响因子：
2
通讯作者：
Kelly, PT
中科院分区：
文献类型：
--
作者：
Wang, JH;Kelly, PT
蛋白激酶和磷酸酶的活性被认为调节大脑中的神经元活动和突触可塑性。大量的体内和体外研究表明，突触强度在基础条件下和长时程增强（LTP）表达期间似乎是稳定的。这可能反映了蛋白激酶和磷酸酶活性之间的平衡。为了给这一假说提供实验证据，并根据我们的知识，即Ca 2 +/CaM激活蛋白激酶和磷酸酶，突触后Ca 2 +/CaM信号通路在突触可塑性中起重要作用，我们研究了突触后Ca 2+依赖性蛋白激酶和钙调神经磷酸酶（CaN）在调节突触强度中的作用。我们发现，抑制海马CA 1神经元突触后Ca 2 +/CaM依赖性蛋白激酶PI（CaM-KII）和Ca 2 +/磷脂酰丝氨酸依赖性蛋白激酶（PKC）可显著减弱LTP的表达，但对基础突触传递无影响。另一方面，抑制突触后CaN可增强和幼稚突触的突触传递，并显着增加LTP诱导期突触增强的幅度。这些结果表明，突触后CaM-K Ⅱ和PKC活性是维持LTP表达所必需的，但CaN活性在基础和增强突触传递期间都将突触强度限制在稳定水平，即蛋白磷酸化和去磷酸化之间的动态平衡设定生理突触强度由CaN活性主导。
The activities of protein kinases and phosphatases are believed to regulate neuronal activity and synaptic plasticity in brain. Numerous in vivo and in vitro studies have shown that synaptic strength appears stable under basal conditions and during long-term potentiation (LTP) expression. This may reflect a balance between protein kinase and phosphatase activities. To provide experimental evidence for this hypothesis, and based on our knowledge that Ca2+/CaM activates protein kinases and phosphatases and that postsynaptic Ca2+/CaM signal pathways play important: roles in synaptic plasticity, we examined the contribution of postsynaptic Ca2+-dependent protein kinases and calcineurin (CaN) in regulating synaptic strength. We show that inhibiting postsynaptic Ca2+/CaM-dependent protein kinase PI (CaM-KII) and Ca2+/phospholipitidyserine-dependent protein kinase (PKC) in hippocampal CA1 neurons attenuates significantly the expression of LTP, but not basal synaptic transmission On the other hand, the inhibition of postsynaptic CaN enhances synaptic transmission at potentiated and naive synapses, and increases significantly the magnitude of synaptic potentiation during the induction phase of LTP. These results indicate that postsynaptic CaM-KII and PKC activities are essential for maintaining LTP expression, bur CaN activity limits synaptic strength at stable levels during both basal and potentiated synaptic transmission that is, the dynamic balance between protein phosphorylation and dephosphorylation that sets physiological synaptic strength is dominated by CaN activity.