PDF(Pubmed)
Abstract：
AMPA-type receptors (AMPARs) are rapidly inserted into synapses undergoing plasticity to increase synaptic transmission, but it is not fully understood if and how AMPAR-containing vesicles are selectively trafficked to these synapses. Here, we developed a strategy to label AMPAR GluA1 subunits expressed from their endogenous loci in cultured rat hippocampal neurons and characterized the motion of GluA1-containing vesicles using single-particle tracking and mathematical modeling. We find that GluA1-containing vesicles are confined and concentrated near sites of stimulation-induced structural plasticity. We show that confinement is mediated by actin polymerization, which hinders the active transport of GluA1-containing vesicles along the length of the dendritic shaft by modulating the rheological properties of the cytoplasm. Actin polymerization also facilitates myosin-mediated transport of GluA1-containing vesicles to exocytic sites. We conclude that neurons utilize F-actin to increase vesicular GluA1 reservoirs and promote exocytosis proximal to the sites of synaptic activity.
摘要：
AMPARA型受体（AMPAR）迅速插入突触经历可塑性，以增加突触传递，但尚不完全了解含AMPAR的囊泡是否以及如何被选择性地贩运到这些突触。这里,我们开发了一种在培养的大鼠海马神经元中标记从内源性基因座表达的AMPARGluA1亚基的策略,并使用单粒子追踪和数学建模表征了含GluA1的囊泡的运动.我们发现含GluA1的囊泡被限制并集中在刺激诱导的结构可塑性位点附近。我们证明限制是由肌动蛋白聚合介导的，通过调节细胞质的流变特性，阻碍了含GluA1的囊泡沿树突状轴长度的主动运输。肌动蛋白聚合还促进肌球蛋白介导的含GluA1的囊泡向外细胞位点的转运。我们得出的结论是，神经元利用F-肌动蛋白来增加囊泡GluA1储库并促进突触活动位点附近的胞吐作用。
