Light-inducible receptor tyrosine kinases that regulate neurotrophin signalling

被引:121
作者
Chang, Ki-Young [1 ,2 ]
Woo, Doyeon [2 ,3 ]
Jung, Hyunjin [2 ]
Lee, Sangkyu [1 ,2 ]
Kim, Sungsoo [2 ]
Won, Joungha [2 ]
Kyung, Taeyoon [2 ]
Park, Hyerim [2 ]
Kim, Nury [1 ,2 ]
Yang, Hee Won [2 ]
Park, Jae-Yong [3 ,4 ,5 ]
Hwang, Eun Mi [3 ]
Kim, Daesoo [2 ]
Do Heo, Won [1 ,2 ]
机构
[1] Inst for Basic Sci, Ctr Cognit & Social, Taejon 305701, South Korea
[2] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea
[3] Korea Inst Sci & Technol, WCI Ctr Funct Connect, Seoul 136791, South Korea
[4] Gyeongsang Natl Univ, Sch Med, Inst Hlth Sci, Dept Neurobiol, Jinju 660751, South Korea
[5] Gyeongsang Natl Univ, Sch Med, Med Res Ctr Neural Dysfunct, Jinju 660751, South Korea
来源
NATURE COMMUNICATIONS | 2014年 / 5卷
基金
新加坡国家研究基金会;
关键词
NERVE GROWTH-FACTOR; PROTEIN INTERACTIONS; TRK RECEPTORS; ACTIVATION; INDUCTION; CELLS; TRANSDUCTION; DIFFERENTIATION; PARTNERS; LIGAND;
D O I
10.1038/ncomms5057
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Receptor tyrosine kinases (RTKs) are a family of cell-surface receptors that have a key role in regulating critical cellular processes. Here, to understand and precisely control RTK signalling, we report the development of a genetically encoded, photoactivatable Trk (tropomyosin-related kinase) family of RTKs using a light-responsive module based on Arabidopsis thaliana cryptochrome 2. Blue-light stimulation (488 nm) of mammalian cells harbouring these receptors robustly upregulates canonical Trk signalling. A single light stimulus triggers transient signalling activation, which is reversibly tuned by repetitive delivery of blue-light pulses. In addition, the light-provoked process is induced in a spatially restricted and cell-specific manner. A prolonged patterned illumination causes sustained activation of extracellular signal-regulated kinase and promotes neurite outgrowth in a neuronal cell line, and induces filopodia formation in rat hippocampal neurons. These light-controllable receptors are expected to create experimental opportunities to spatiotemporally manipulate many biological processes both in vitro and in vivo.
引用
收藏
页数:10
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