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Light-inducible receptor tyrosine kinases that regulate neurotrophin signalling.

Nature communications (2014-06-05)
Ki-Young Chang, Doyeon Woo, Hyunjin Jung, Sangkyu Lee, Sungsoo Kim, Joungha Won, Taeyoon Kyung, Hyerim Park, Nury Kim, Hee Won Yang, Jae-Yong Park, Eun Mi Hwang, Daesoo Kim, Won Do Heo

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.

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