AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity.
AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity.
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DOI：
10.7554/elife.30640
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发表时间：
2017-11-27
期刊：
影响因子：
7.7
通讯作者：
Hoeffer CA
中科院分区：
文献类型：
--
作者：
Levenga J;Wong H;Milstead RA;Keller BN;LaPlante LE;Hoeffer CA
AKT是一种调节脑中许多细胞过程的激酶，已知AKT的突变会影响脑功能。AKT间接参与突触可塑性，但其直接作用尚未研究。此外，三种高度相关的AKT亚型在大脑中表达，但它们各自的作用知之甚少。我们发现在小家鼠中，每个AKT亚型在海马中具有独特的表达模式，AKT 1和AKT 3主要在神经元中，但显示局部差异，而AKT 2在星形胶质细胞中。我们还发现AKT在CA 1区海马突触可塑性的多个范例中的亚型特异性作用。AKT 1，而不是AKT 2或AKT 3，是L-LTP通过调节活性诱导的蛋白质合成所必需的。有趣的是，AKT活性抑制mGluR-LTD，对AKT 1和AKT 3具有重叠功能。总之，我们的研究确定了海马AKT亚型在突触可塑性中的不同表达模式和作用。
AKT is a kinase regulating numerous cellular processes in the brain, and mutations in AKT are known to affect brain function. AKT is indirectly implicated in synaptic plasticity, but its direct role has not been studied. Moreover, three highly related AKT isoforms are expressed in the brain, but their individual roles are poorly understood. We find in Mus musculus, each AKT isoform has a unique expression pattern in the hippocampus, with AKT1 and AKT3 primarily in neurons but displaying local differences, while AKT2 is in astrocytes. We also find isoform-specific roles for AKT in multiple paradigms of hippocampal synaptic plasticity in area CA1. AKT1, but not AKT2 or AKT3, is required for L-LTP through regulating activity-induced protein synthesis. Interestingly, AKT activity inhibits mGluR-LTD, with overlapping functions for AKT1 and AKT3. In summary, our studies identify distinct expression patterns and roles in synaptic plasticity for AKT isoforms in the hippocampus.