The Regulation of AMPA Receptor Endocytosis by Dynamic Protein-Protein Interactions.

The Regulation of AMPA Receptor Endocytosis by Dynamic Protein-Protein Interactions.
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通过动态蛋白 - 蛋白质相互作用调节AMPA受体内吞作用。

DOI:
10.3389/fncel.2018.00362
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发表时间:
2018
影响因子:
5.3
通讯作者:
Hanley JG
Hanley JG
中科院分区:
医学2区
文献类型:
--
作者:
Hanley JG

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神经元中AMPA受体(AMPAR)运输的精确调控对于兴奋性神经传递、突触可塑性以及大脑发育和学习过程中神经回路的形成和改变至关重要。网格蛋白介导的内吞作用(CME)是神经元质膜上依赖活性去除AMPA受体的一种重要运输活动,会导致突触强度降低,即长时程抑制(LTD)。构成LTD基础的受调控的AMPA受体内吞作用是由特定的突触活动模式引起的,最显著的是N - 甲基 - D - 天冬氨酸受体(NMDARs)和代谢型谷氨酸受体(mGluRs)的刺激。许多蛋白质直接或间接与AMPA受体亚基结合以控制其运输,因此,响应NMDAR或mGluR信号对这些蛋白质 - 蛋白质相互作用的调控是突触可塑性的一个关键特征。本文综述了在突触可塑性过程中动态调控以调节AMPA受体内吞作用的蛋白质 - 蛋白质相互作用,重点关注AMPA受体结合蛋白以及与核心内吞机制结合的蛋白质。此外,还考虑了蛋白质 - 蛋白质相互作用的调控机制,以及这些动态相互作用对AMPA受体内吞作用的功能影响。
The precise regulation of AMPA receptor (AMPAR) trafficking in neurons is crucial for excitatory neurotransmission, synaptic plasticity and the consequent formation and modification of neural circuits during brain development and learning. Clathrin-mediated endocytosis (CME) is an essential trafficking event for the activity-dependent removal of AMPARs from the neuronal plasma membrane, resulting in a reduction in synaptic strength known as long-term depression (LTD). The regulated AMPAR endocytosis that underlies LTD is caused by specific modes of synaptic activity, most notably stimulation of NMDA receptors (NMDARs) and metabotropic glutamate receptors (mGluRs). Numerous proteins associate with AMPAR subunits, directly or indirectly, to control their trafficking, and therefore the regulation of these protein-protein interactions in response to NMDAR or mGluR signaling is a critical feature of synaptic plasticity. This article reviews the protein-protein interactions that are dynamically regulated during synaptic plasticity to modulate AMPAR endocytosis, focussing on AMPAR binding proteins and proteins that bind the core endocytic machinery. In addition, the mechanisms for the regulation of protein-protein interactions are considered, as well as the functional consequences of these dynamic interactions on AMPAR endocytosis.
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