Construction of Light-Activated Neurotrophin Receptors Using the Improved Light-Induced Dimerizer (iLID).
Construction of Light-Activated Neurotrophin Receptors Using the Improved Light-Induced Dimerizer (iLID).
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DOI：
10.1016/j.jmb.2020.04.018
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发表时间：
2020-06-12
影响因子：
5.6
通讯作者：
Cui, Bianxiao
中科院分区：
文献类型：
--
作者：
Hope, Jen M.;Liu, Aofei;Calvin, Ghawayne J.;Cui, Bianxiao
Receptor tyrosine kinases (RTKs) play crucial roles in human health, and their misregulation is implicated in disorders ranging from neurodegenerative diseases to cancers. The highly conserved mechanism of activation of RTKs makes them especially appealing candidates for control via optogenetic dimerization methods. This work offers a strategy for using the improved light-induced dimer (iLID) system with a constructed tandem dimer of its binding partner nano (tdnano) to build light-activatable versions of RTKs. In the absence of light, the iLID-RTK is cytosolic, monomeric, and inactive. Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing, and activating the RTK. We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano. We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells. By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination, allowing us to confidently probe the impact of context on signaling outcome.
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影响因子：
64.5
作者：
Regot S;Hughey JJ;Bajar BT;Carrasco S;Covert MW
通讯作者：
Covert MW
影响因子：
48
作者：
Kennedy, Matthew J.;Hughes, Robert M.;Peteya, Leslie A.;Schwartz, Joel W.;Ehlers, Michael D.;Tucker, Chandra L.
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Tucker, Chandra L.
影响因子：
4.7
作者：
Duan, Liting;Hope, Jen M.;Cui, Bianxiao
通讯作者：
Cui, Bianxiao
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2.4
作者：
Locke C;Machida K;Tucker CL;Wu Y;Yu J
通讯作者：
Yu J
影响因子：
4.7
作者：
Che, Daphne L.;Duan, Liting;Cui, Bianxiao
通讯作者：
Cui, Bianxiao