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.
authors.affiliation: 1] 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].
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Chang
authors.affiliation: 1] Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea [2] WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea [3].
authors.forename: Doyeon
authors.initials: D
authors.lastname: Woo
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Jung
authors.affiliation: 1] 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.
authors.forename: Sangkyu
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Sungsoo
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Joungha
authors.initials: J
authors.lastname: Won
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Taeyoon
authors.initials: T
authors.lastname: Kyung
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Hyerim
authors.initials: H
authors.lastname: Park
authors.affiliation: 1] 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.
authors.forename: Nury
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Hee Won
authors.initials: HW
authors.lastname: Yang
authors.affiliation: 1] WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea [2] Department of Neurobiology, Institute of Health Science, and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hwang
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Daesoo
authors.initials: D
authors.lastname: Kim
authors.affiliation: 1] 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.
authors.forename: Won Do
authors.initials: WD
authors.lastname: Heo
mesh_terms: D000818:Animals; D017360:Arabidopsis; D029681:Arabidopsis Proteins / Q000235:genetics; D002460:Cell Line; D056931:Cryptochromes / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008027:Light; D009414:Nerve Growth Factors / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020917:Receptor, trkA / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D020812:Receptor, trkC / Q000378:metabolism
chemical_list: D029681:Arabidopsis Proteins; D056931:Cryptochromes; D009414:Nerve Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC