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

Williams, Daniel C., El Bejjani, Rachid, Mugno Ramirez, Paula, Coakley, Sean, Kim, Shin Ae, Lee, Hyewon, Wen, Quan, Samuel, Aravi, Lu, Hang, Hilliard, Massimo A. and Hammarlund, Marc (2013) Rapid and permanent neuronal inactivation in vivo via subcellular generation of reactive oxygen with the use of KillerRed. Cell Reports, 5 2: 553-563. doi:10.1016/j.celrep.2013.09.023

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Author Williams, Daniel C.
El Bejjani, Rachid
Mugno Ramirez, Paula
Coakley, Sean
Kim, Shin Ae
Lee, Hyewon
Wen, Quan
Samuel, Aravi
Lu, Hang
Hilliard, Massimo A.
Hammarlund, Marc
Title Rapid and permanent neuronal inactivation in vivo via subcellular generation of reactive oxygen with the use of KillerRed
Journal name Cell Reports   Check publisher's open access policy
ISSN 2211-1247
Publication date 2013-10-31
Sub-type Article (original research)
DOI 10.1016/j.celrep.2013.09.023
Open Access Status DOI
Volume 5
Issue 2
Start page 553
End page 563
Total pages 11
Place of publication New York, NY, United States
Publisher Elsevier
Collection year 2014
Language eng
Formatted abstract
Highlights
• KillerRed activation causes immediate and permanent silencing of neuronal function
• KillerRed can be used to acutely manipulate neuronal circuits
• KillerRed activation results in cell death of targeted neurons
• Localizing KillerRed to mitochondria produces organelle-specific effects

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 the 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 the 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 and subcellular responses to ROS.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 18 times in Scopus Article | Citations
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Created: Wed, 13 Nov 2013, 13:23:25 EST by Debra McMurtrie on behalf of Queensland Brain Institute