Rapid and permanent neuronal inactivation in vivo via subcellular generation of reactive oxygen with the use of KillerRed.

Rapid and permanent neuronal inactivation in vivo via subcellular generation of reactive oxygen with the use of KillerRed.
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DOI:
10.1016/j.celrep.2013.09.023
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发表时间:
2013-10-31
期刊:
影响因子:
8.8
通讯作者:
Hammarlund M
Hammarlund M
中科院分区:
生物学1区
文献类型:
--
作者:
Williams DC;Bejjani RE;Ramirez PM;Coakley S;Kim SA;Lee H;Wen Q;Samuel A;Lu H;Hilliard MA;Hammarlund M

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Inactivation of selected neurons in vivo can define their contribution to specific developmental outcomes, circuit functions, and behaviors. Here, we show that the optogenetic tool KillerRed selectively, rapidly, and permanently inactivates different classes of neurons in C. elegans in response to a single light stimulus, through generation of reactive oxygen species (ROS). Ablation scales from individual neurons in single animals to multiple neurons in populations, and can be applied to freely behaving animals. Using spatially restricted illumination, we demonstrate that localized KillerRed activation in either the cell body or the axon triggers neuronal degeneration and death of the targeted cell. Finally, targeting KillerRed to mitochondria results in organelle fragmentation without killing the cell, in contrast to cell death observed when KillerRed is targeted to the plasma membrane. We expect this genetic tool to have wide-ranging applications in studies of circuit function, as well as of sub-cellular responses to ROS.
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