Research Abstract


Chemical labelling for visualizing native AMPA receptors in live neurons

2017年4月7日 Nature Communications 8 : 14850 doi: 10.1038/ncomms14850



Sho Wakayama, Shigeki Kiyonaka, Itaru Arai, Wataru Kakegawa, Shinji Matsuda, Keiji Ibata, Yuri L. Nemoto, Akihiro Kusumi, Michisuke Yuzaki and Itaru Hamachi

Corresponding Authors

京都大学大学院 工学研究科 合成・生物化学専攻

京都大学大学院 工学研究科 合成・生物化学専攻

The location and number of neurotransmitter receptors are dynamically regulated at postsynaptic sites. However, currently available methods for visualizing receptor trafficking require the introduction of genetically engineered receptors into neurons, which can disrupt the normal functioning and processing of the original receptor. Here we report a powerful method for visualizing native α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) which are essential for cognitive functions without any genetic manipulation. This is based on a covalent chemical labelling strategy driven by selective ligand-protein recognition to tether small fluorophores to AMPARs using chemical AMPAR modification (CAM) reagents. The high penetrability of CAM reagents enables visualization of native AMPARs deep in brain tissues without affecting receptor function. Moreover, CAM reagents are used to characterize the diffusion dynamics of endogenous AMPARs in both cultured neurons and hippocampal slices. This method will help clarify the involvement of AMPAR trafficking in various neuropsychiatric and neurodevelopmental disorders.