Positioning of AMPA Receptor-Containing Endosomes Regulates Synapse Architecture
Positioning of AMPA Receptor-Containing Endosomes Regulates Synapse Architecture
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DOI：
10.1016/j.celrep.2015.09.062
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发表时间：
2015-11-03
期刊：
影响因子：
8.8
通讯作者：
Hoogenraad, Casper C.
中科院分区：
文献类型：
--
作者：
da Silva, Marta Esteves;Adrian, Max;Hoogenraad, Casper C.
膜的侧向扩散和内体转运都有助于突触后部位AMPA受体(AMPAR)的增加和移除。然而，这些机制之间的空间协调仍然不清楚，因为人们对含有AMPAR的内小体的动力学知之甚少。此外，含有AMPAR的内小体的位置如何影响突触的组织和功能从未被直接探索过。在这里，我们使用海马神经元培养的活细胞成像来表明细胞内的AMPAR是通过Rab11阳性的循环内小体运输的，这些内小体经常进入树突棘并依赖于微管和肌动蛋白细胞骨架。通过使用化学诱导的二聚系统将驱动蛋白(KIF1C)或肌球蛋白(MyosinV/VI)马达募集到Rab11阳性的循环内小体，我们控制了它们的运输，发现诱导从脊柱上移除循环内小体会减少表面AMPAR的表达和突触上的PSD-95簇。我们的数据表明，内小体定位与突触后结构和组成之间存在机械联系。
Lateral diffusion in the membrane and endosomal trafficking both contribute to the addition and removal of AMPA receptors (AMPARs) at postsynaptic sites. However, the spatial coordination between these mechanisms has remained unclear, because little is known about the dynamics of AMPAR-containing endosomes. In addition, how the positioning of AMPAR-containing endosomes affects synapse organization and functioning has never been directly explored. Here, we used live-cell imaging in hippocampal neuron cultures to show that intracellular AMPARs are transported in Rab11-positive recycling endosomes, which frequently enter dendritic spines and depend on the microtubule and actin cytoskeleton. By using chemically induced dimerization systems to recruit kinesin (KIF1C) or myosin (MyosinV/VI) motors to Rab11-positive recycling endosomes, we controlled their trafficking and found that induced removal of recycling endosomes from spines decreases surface AMPAR expression and PSD-95 clusters at synapses. Our data suggest a mechanistic link between endosome positioning and postsynaptic structure and composition.