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bioRxiv · 10.1101/2020.05.04.075564

A GRAB sensor reveals activity-dependent non-vesicular somatodendritic adenosine release

Wu, Z.·Cui, Y.·Wang, H.·Song, K.·Yuan, Z.·Dong, A.·Wu, H.·Wan, Y.·Pan, S.·Peng, W.·Jing, M.·Xu, M.·Luo, M.·Li, Y.
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Abstract

The purinergic signaling molecule adenosine (Ado) modulates many physiological and pathological brain functions,but its spatiotemporal release dynamics in the brain remains largely unknown. We developed a genetically encoded GPCR-Activation-Based Ado sensor (GRABAdo) in which Ado-induced changes in the human A2A receptor are reflected by fluorescence increases. This GRABAdo revealed that neuronal activity-induced extracellular Ado elevation was due to direct Ado release from somatodendritic regions of the neuron, requiring calcium influx through L-type calcium channels, rather than the degradation of extracellular ATP. The Ado release was slow ([~]30 s) and depended on equilibrative nucleoside transporters (ENTs) rather than conventional vesicular release mechanisms. Thus, GRABAdo reveals an activity-dependent slow Ado release from somatodendritic region of the neuron, potentially serving modulating functions as a retrograde signal.

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Wu, Z., Cui, Y., Wang, H., Song, K., Yuan, Z., Dong, A., Wu, H., Wan, Y., Pan, S., Peng, W., Jing, M., Xu, M., Luo, M., Li, Y.. 2020-05-05. A GRAB sensor reveals activity-dependent non-vesicular somatodendritic adenosine release. https://doi.org/10.1101/2020.05.04.075564

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