期刊
ELIFE
卷 10, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.64714
关键词
-
类别
资金
- Wellcome Trust [212251_Z_18_Z]
- National Science Centre Poland [2017/26/D/NZ3/01017]
- European Research Council [323113]
- European Commission [857562]
By generating its pH-sensitive fluorescent analogue GLT1-SEP, researchers visualized the dynamics of the main glial glutamate transporter GLT1 in astrocyte membrane, revealing its surface dwell time and turnover pattern. The results show that membrane turnover is the main 'redeployment' route for the immobile fraction of surface-expressed GLT1, helping to control extrasynaptic escape of glutamate.
Glutamate uptake by astroglial transporters confines excitatory transmission to the synaptic cleft. The efficiency of this mechanism depends on the transporter dynamics in the astrocyte membrane, which remains poorly understood. Here, we visualise the main glial glutamate transporter GLT1 by generating its pH-sensitive fluorescent analogue, GLT1-SEP. Fluorescence recovery after photobleaching-based imaging shows that 70-75% of GLT1-SEP dwell on the surface of rat brain astroglia, recycling with a lifetime of similar to 22 s. Genetic deletion of the C-terminus accelerates GLT1-SEP membrane turnover while disrupting its surface pattern, as revealed by single-molecule localisation microscopy. Excitatory activity boosts surface mobility of GLT1-SEP, involving its C-terminus, metabotropic glutamate receptors, intracellular Ca2+, and calcineurin-phosphatase activity, but not the broad-range kinase activity. The results suggest that membrane turnover, rather than lateral diffusion, is the main 'redeployment' route for the immobile fraction (20-30%) of surface-expressed GLT1. This finding reveals an important mechanism helping to control extrasynaptic escape of glutamate.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据