Actin-dependent mechanisms in AMPA receptor trafficking.

Actin-dependent mechanisms in AMPA receptor trafficking.
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DOI:
10.3389/fncel.2014.00381
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发表时间:
2014
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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突触处AMPA受体(AMPAR)数量和亚型的精确调控对于兴奋性神经传递、突触可塑性以及随后形成适合学习和记忆的神经回路至关重要。AMPAR的运输涉及胞吐作用、胞吞作用和内体再循环的动态过程,所有这些过程都涉及肌动蛋白细胞骨架。肌动蛋白细胞骨架具有高度动态性,并受到大量肌动蛋白结合蛋白和上游信号通路的高度调控,这些蛋白和通路调节肌动蛋白的聚合和解聚。肌动蛋白动力学在囊泡生物发生过程中产生操纵膜的力,并且还用于推动囊泡穿过细胞质到达其目的地。此外,运输机制通过利用基于肌动蛋白的马达蛋白沿着肌动蛋白丝运输囊泡货物,从而利用肌动蛋白细胞骨架更稳定的方面。大量研究表明,肌动蛋白动力学对于AMPAR的定位和功能至关重要。对与AMPAR亚基发生物理相互作用的肌动蛋白结合蛋白的鉴定以及对其作用方式的研究开始揭示所涉及的机制。这类蛋白要么调节肌动蛋白动力学以调节施加在含AMPAR的膜上的机械力,要么与肌动蛋白丝结合以将含AMPAR的囊泡靶向或运输到特定的亚细胞区域。此外,不与AMPAR发生物理相互作用的肌动蛋白调节蛋白可能通过调节树突棘中的局部肌动蛋白环境来影响AMPAR的运输。
The precise regulation of AMPA receptor (AMPAR) number and subtype at the synapse is crucial for the regulation of excitatory neurotransmission, synaptic plasticity and the consequent formation of appropriate neural circuits for learning and memory. AMPAR trafficking involves the dynamic processes of exocytosis, endocytosis and endosomal recycling, all of which involve the actin cytoskeleton. The actin cytoskeleton is highly dynamic and highly regulated by an abundance of actin-binding proteins and upstream signaling pathways that modulate actin polymerization and depolymerization. Actin dynamics generate forces that manipulate membranes in the process of vesicle biogenesis, and also for propelling vesicles through the cytoplasm to reach their destination. In addition, trafficking mechanisms exploit more stable aspects of the actin cytoskeleton by using actin-based motor proteins to traffic vesicular cargo along actin filaments. Numerous studies have shown that actin dynamics are critical for AMPAR localization and function. The identification of actin-binding proteins that physically interact with AMPAR subunits, and research into their mode of action is starting to shed light on the mechanisms involved. Such proteins either regulate actin dynamics to modulate mechanical forces exerted on AMPAR-containing membranes, or associate with actin filaments to target or transport AMPAR-containing vesicles to specific subcellular regions. In addition, actin-regulatory proteins that do not physically interact with AMPARs may influence AMPAR trafficking by regulating the local actin environment in the dendritic spine.
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