Activity-dependent PI4P synthesis by PI4KIIIα regulates long-term synaptic potentiation
Activity-dependent PI4P synthesis by PI4KIIIα regulates long-term synaptic potentiation
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PI4KIIIα 的活动依赖性 PI4P 合成调节长期突触增强
DOI：
10.1016/j.celrep.2022.110452
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发表时间：
2022-03-01
期刊：
影响因子：
8.8
通讯作者：
Liu，Jia-Jia
中科院分区：
文献类型：
--
作者：
Guo，Zhenzhen;Jiang，Chao-Hua;Liu，Jia-Jia
Phosphatidylinositol 4-phosphate (PI4P) is a low abundant phospholipid with important roles in lipid transport and membrane trafficking. However, little is known of its metabolism and function in neurons. Here, we investigate its subcellular distribution and functional roles in dendrites of rodent hippocampal neurons during resting state and long-term synaptic potentiation (LTP). We show that neural activity causes dynamic reversible changes in PI4P metabolism in dendrites. Upon LTP induction, PI4KIIIα, a type III phosphatidylinositol 4-kinase, localizes to the dendritic plasma membrane (PM) in a calcium-dependent manner and causes substantial increase in the levels of PI4P. Acute inhibition of PI4KIIIα activity abolishes trafficking of the AMPA-type glutamate receptor to the PM during LTP induction, and silencing of PI4KIIIα expression in the hippocampal CA1 region causes severe impairment of LTP and long-term memory. Collectively, our results identify an essential role for PI4KIIIα-dependent PI4P synthesis in synaptic plasticity of central nervous system neurons.
