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Published on: July 11, 2020
Light-inducible receptor tyrosine kinases that regulate neurotrophin signalling
Ki-Young Chang1, Doyeon Woo2, Hyunjin Jung3
11] Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon 305-701, Republic of Korea [2] Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea [3].
Abstract:
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.
Insights
Scientists developed light-controllable receptor tyrosine kinases (RTKs) for precise cell signaling control. Blue light activates Trk signaling, enabling spatiotemporal manipulation of cellular processes in vitro and in vivo.
Area of Science:
- Molecular Biology
- Cell Signaling
- Biotechnology
Background:
- Receptor tyrosine kinases (RTKs) are crucial cell-surface receptors regulating vital cellular processes.
- Precise control over RTK signaling is essential for understanding and manipulating cellular functions.
Purpose of the Study:
- To develop a genetically encoded, photoactivatable Trk (tropomyosin-related kinase) receptor system.
- To enable precise spatiotemporal control of RTK signaling using blue light.
Main Methods:
- Engineered photoactivatable Trk receptors using Arabidopsis thaliana cryptochrome 2.
- Utilized blue-light stimulation (488 nm) to activate Trk signaling in mammalian cells.
- Investigated transient and sustained signaling activation, spatial restriction, and cell-specific induction.
Main Results:
- Blue-light stimulation robustly upregulated canonical Trk signaling.
- Signaling activation was transient, reversible, and tunable with light pulses.
- Light-induced signaling occurred in a spatially restricted and cell-specific manner.
- Sustained activation promoted neurite outgrowth and filopodia formation in neurons.
Conclusions:
- Developed a novel system for light-inducible control of Trk RTK signaling.
- Demonstrated spatiotemporal manipulation of cellular processes, including neuronal morphology.
- This technology offers new experimental avenues for studying and controlling biological processes in vitro and in vivo.
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