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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Loss of AKAP150 perturbs distinct neuronal processes in mice
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Loss of AKAP150 perturbs distinct neuronal processes in mice

机译：AKAP150的丢失扰乱了小鼠中独特的神经元过程

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摘要

A-Kinase Anchoring Proteins (AKAPs) ensure the fidelity of second messenger signaling events by directing protein kinases and phos-phatases toward their preferred substrates. AKAP150 brings protein kinase A (PKA), the calcium/calmodulin dependent phospha-tase PP26 and protein kinase C (PKC) to postsynaptic membranes where they facilitate the phosphorylation dependent modulation of certain ion channels. Immunofluorescence and electrophysio-logical recordings were combined with behavioral analyses to assess whether removal of AKAP150 by gene targeting in mice changes the signaling environment to affect excitatory and inhibitory neuronal processes. Mislocalization of PKA in AKAP150 null hippocampal neurons alters the bidirectional modulation of postsynaptic AMPA receptors with concomitant changes in synap-tic transmission and memory retention. AKAP150 null mice also exhibit deficits in motor coordination and strength that are consistent with a role for the anchoring protein in the cerebellum. Loss of AKAP150 in sympathetic cervical ganglion (SCG) neurons reduces muscarinic suppression of inhibitory M currents and provides these animals with a measure of resistance to seizures induced by the non-selective muscarinic agonist pilocarpine. These studies argue that distinct AKAP150-enzyme complexes regulate context-dependent neuronal signaling events in vivo.
机译：A激酶锚定蛋白（AKAP）通过将蛋白激酶和磷酸酶引导至它们的优选底物来确保第二信使信号传递事件的保真度。 AKAP150将蛋白激酶A（PKA），钙/钙调蛋白依赖性磷酸酶PP26和蛋白激酶C（PKC）带到突触后膜，在突触后膜上促进某些离子通道的磷酸化依赖性调节。免疫荧光和电生理学记录与行为分析相结合，以评估通过基因靶向小鼠清除AKAP150是否会改变信号传导环境，从而影响兴奋性和抑制性神经元过程。 AKAP150空海马神经元中PKA的定位错误会改变突触后AMPA受体的双向调节，并伴随突触传递和记忆力的改变。 AKAP150无效的小鼠还表现出运动协调和强度的缺陷，这与小脑中锚定蛋白的作用一致。交感性颈神经节（SCG）神经元中AKAP150的丢失会降低毒蕈碱抑制性M电流的抑制作用，并为这些动物提供对非选择性毒蕈碱激动剂毛果芸香碱诱发的癫痫发作的抵抗力。这些研究认为，不同的AKAP150酶复合物调节体内上下文相关的神经元信号事件。

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