Light-inducible receptor tyrosine kinases that regulate neurotrophin signalling

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

doi:10.1038/ncomms5057

Light-inducible receptor tyrosine kinases that regulate neurotrophin signalling

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

Research output: Contribution to journal › Article › peer-review

90 Citations (Scopus)

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.

Original language	English
Article number	4057
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5057
Publication status	Published - 2014 Jun 4
Externally published	Yes

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/ncomms5057

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Light-inducible receptor tyrosine kinases that regulate neurotrophin signalling. / Chang, Ki Young; Woo, Doyeon; Jung, Hyunjin; Lee, Sangkyu; Kim, Sungsoo; Won, Joungha; Kyung, Taeyoon; Park, Hyerim; Kim, Nury; Yang, Hee Won; Park, Jae Yong; Hwang, Eun Mi; Kim, Daesoo; Do Heo, Won.

In: Nature communications, Vol. 5, 4057, 04.06.2014.

Research output: Contribution to journal › Article › peer-review

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title = "Light-inducible receptor tyrosine kinases that regulate neurotrophin signalling",

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.",

author = "Chang, {Ki Young} and Doyeon Woo and Hyunjin Jung and Sangkyu Lee and Sungsoo Kim and Joungha Won and Taeyoon Kyung and Hyerim Park and Nury Kim and Yang, {Hee Won} and Park, {Jae Yong} and Hwang, {Eun Mi} and Daesoo Kim and {Do Heo}, Won",

note = "Funding Information: We thank K. Kaibuchi, L. C. Schecterson, and C. L. Tucker for sharing plasmids. In addition, we thank Su Yeon Choi from Eunjoon Kim{\textquoteright}s laboratory at IBS/KAIST and Seock Kang from Myoung-Goo Kang{\textquoteright}s laboratory at IBS for guiding us how to culture rat primary hippocampal neurons. This work was supported by the National Research Foundation of Korea Stem Cell Program (no. 2011-0019509), the Intelligent Synthetic Biology Center of Global Frontier Project (no. 2011-0031955), the National Leading Research Laboratory Program (to D.K.; 2011-0028772), the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and Future Planning (2010-0027941) and the Korea Advanced Institute of Science and Technology Future Systems Healthcare Project funded by the Ministry of Science, Information and Communication Technology & Future Planning in Korea.",

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AU - Chang, Ki Young

AU - Woo, Doyeon

AU - Jung, Hyunjin

AU - Lee, Sangkyu

AU - Kim, Sungsoo

AU - Won, Joungha

AU - Kyung, Taeyoon

AU - Park, Hyerim

AU - Kim, Nury

AU - Yang, Hee Won

AU - Park, Jae Yong

AU - Hwang, Eun Mi

AU - Kim, Daesoo

AU - Do Heo, Won

N1 - Funding Information: We thank K. Kaibuchi, L. C. Schecterson, and C. L. Tucker for sharing plasmids. In addition, we thank Su Yeon Choi from Eunjoon Kim’s laboratory at IBS/KAIST and Seock Kang from Myoung-Goo Kang’s laboratory at IBS for guiding us how to culture rat primary hippocampal neurons. This work was supported by the National Research Foundation of Korea Stem Cell Program (no. 2011-0019509), the Intelligent Synthetic Biology Center of Global Frontier Project (no. 2011-0031955), the National Leading Research Laboratory Program (to D.K.; 2011-0028772), the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and Future Planning (2010-0027941) and the Korea Advanced Institute of Science and Technology Future Systems Healthcare Project funded by the Ministry of Science, Information and Communication Technology & Future Planning in Korea.

PY - 2014/6/4

Y1 - 2014/6/4

N2 - 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.

AB - 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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JO - Nature Communications

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Light-inducible receptor tyrosine kinases that regulate neurotrophin signalling

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