Protein kinase D promotes activity-dependent AMPA receptor endocytosis in hippocampal neurons,Traffic

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Protein kinase D promotes activity-dependent AMPA receptor endocytosis in hippocampal neurons
Traffic ( IF 3.6 ) Pub Date : 2021-09-26 , DOI: 10.1111/tra.12819
Carlos O Oueslati Morales ₁ , Attila Ignácz ₂ , Norbert Bencsik ₂ , Zsofia Sziber ₂ , Anikó Erika Rátkai ₂ , Wolfgang S Lieb ₁ , Stephan A Eisler ₃ , Attila Szűcs ₂ , Katalin Schlett ₂ , Angelika Hausser _{1,

3}

Affiliation

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamate receptors (AMPARs) mediate the majority of fast excitatory neurotransmission in the brain. The continuous trafficking of AMPARs into and out of synapses is a core feature of synaptic plasticity, which is considered as the cellular basis of learning and memory. The molecular mechanisms underlying the postsynaptic AMPAR trafficking, however, are still not fully understood. In this work, we demonstrate that the protein kinase D (PKD) family promotes basal and activity-induced AMPAR endocytosis in primary hippocampal neurons. Pharmacological inhibition of PKD increased synaptic levels of GluA1-containing AMPARs, slowed down their endocytic trafficking and increased neuronal network activity. By contrast, ectopic expression of constitutive active PKD decreased the synaptic level of AMPARs, while increasing their colocalization with early endosomes. Our results thus establish an important role for PKD in the regulation of postsynaptic AMPAR trafficking during synaptic plasticity.

中文翻译：

蛋白激酶 D 促进海马神经元中活性依赖性 AMPA 受体的内吞作用

α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA) 型谷氨酸受体 (AMPAR) 介导大脑中大部分的快速兴奋性神经传递。AMPAR 不断进出突触是突触可塑性的核心特征，被认为是学习和记忆的细胞基础。然而，突触后 AMPAR 贩运的分子机制仍未完全了解。在这项工作中，我们证明了蛋白激酶 D (PKD) 家族在原代海马神经元中促进基础和活性诱导的 AMPAR 内吞作用。PKD 的药理学抑制增加了含有 GluA1 的 AMPAR 的突触水平，减缓了它们的内吞运输并增加了神经元网络活动。相比之下，组成型活性PKD的异位表达降低了AMPAR的突触水平，同时增加了它们与早期内体的共定位。因此，我们的结果确立了 PKD 在突触可塑性期间调节突触后 AMPAR 运输的重要作用。

更新日期：2021-11-19

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