PhotonSABER: new tool shedding light on endocytosis and learning mechanisms in vivo

PhotonSABER: new tool shedding light on endocytosis and learning mechanisms in vivo
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PhotonSABER:揭示体内内吞作用和学习机制的新工具

DOI:
10.1080/19420889.2019.1586048
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发表时间:
2019
影响因子:
--
通讯作者:
Yuzaki Michisuke
Yuzaki Michisuke
中科院分区:
--
文献类型:
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作者:
Matsuda Shinji;Kakegawa Wataru;Yuzaki Michisuke

文献摘要

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在中枢神经系统中,突触后 AMPA 型谷氨酸受体(AMPA 受体)的活动依赖性内吞作用被认为可介导长期抑郁(LTD),这是各种神经元回路中的突触可塑性模型。然而,特定突触处的 AMPA 受体内吞作用和 LTD 是否以及如何与体内学习和记忆存在因果关系仍不清楚。最近,我们开发了一种新的光遗传学工具 PhotonSABER,它可以在激活的突触处以时间、空间和细胞类型特异性的方式控制 AMPA 受体内吞作用。使用 PhotonSABER,我们发现小脑平行纤维和浦肯野细胞之间突触的 AMPA 受体内吞作用和 LTD 介导动眼神经学习。我们还发现 PhotonSABER 在光刺激下可以抑制 HeLa 细胞中表皮生长因子受体的内吞作用。这些结果表明,PhotonSABER 是分析非神经元细胞内吞作用的生理功能以及 LTD 在各个大脑区域中的作用的强大工具。
In the central nervous system, activity-dependent endocytosis of postsynaptic AMPA-type glutamate receptors (AMPA receptors) is thought to mediate long-term depression (LTD), which is a synaptic plasticity model in various neuronal circuits. However, whether and how AMPA receptor endocytosis and LTD at specific synapses are causally linked to learning and memoryin vivoremains unclear. Recently, we developed a new optogenetic tool, PhotonSABER, which could control AMPA receptor endocytosis in temporal, spatial, and cell-type-specific manners at activated synapses. Using PhotonSABER, we found that AMPA receptor endocytosis and LTD at synapses between parallel fibers and Purkinje cells in the cerebellum mediate oculomotor learning. We also found that PhotonSABER could inhibit endocytosis of epidermal growth factor receptors in HeLa cells upon light stimulation. These results demonstrate that PhotonSABER is a powerful tool for analyzing the physiological functions of endocytosis in non-neuronal cells, as well as the roles of LTD in various brain regions.