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Neurotrophin receptor tyrosine kinases regulated with near-infrared light

Optical control over the activity of receptor tyrosine kinases (RTKs) provides an efficient way to reversibly and non-invasively map their functions. We combined catalytic domains of Trk (tropomyosin receptor kinase) family of RTKs, naturally activated by neurotrophins, with photosensory core module...

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Autores principales: Leopold, Anna V., Chernov, Konstantin G., Shemetov, Anton A., Verkhusha, Vladislav V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408446/
https://www.ncbi.nlm.nih.gov/pubmed/30850602
http://dx.doi.org/10.1038/s41467-019-08988-3
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author Leopold, Anna V.
Chernov, Konstantin G.
Shemetov, Anton A.
Verkhusha, Vladislav V.
author_facet Leopold, Anna V.
Chernov, Konstantin G.
Shemetov, Anton A.
Verkhusha, Vladislav V.
author_sort Leopold, Anna V.
collection PubMed
description Optical control over the activity of receptor tyrosine kinases (RTKs) provides an efficient way to reversibly and non-invasively map their functions. We combined catalytic domains of Trk (tropomyosin receptor kinase) family of RTKs, naturally activated by neurotrophins, with photosensory core module of DrBphP bacterial phytochrome to develop opto-kinases, termed Dr-TrkA and Dr-TrkB, reversibly switchable on and off with near-infrared and far-red light. We validated Dr-Trk ability to reversibly light-control several RTK pathways, calcium level, and demonstrated that their activation triggers canonical Trk signaling. Dr-TrkA induced apoptosis in neuroblastoma and glioblastoma, but not in other cell types. Absence of spectral crosstalk between Dr-Trks and blue-light-activatable LOV-domain-based translocation system enabled intracellular targeting of Dr-TrkA independently of its activation, additionally modulating Trk signaling. Dr-Trks have several superior characteristics that make them the opto-kinases of choice for regulation of RTK signaling: high activation range, fast and reversible photoswitching, and multiplexing with visible-light-controllable optogenetic tools.
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spelling pubmed-64084462019-03-11 Neurotrophin receptor tyrosine kinases regulated with near-infrared light Leopold, Anna V. Chernov, Konstantin G. Shemetov, Anton A. Verkhusha, Vladislav V. Nat Commun Article Optical control over the activity of receptor tyrosine kinases (RTKs) provides an efficient way to reversibly and non-invasively map their functions. We combined catalytic domains of Trk (tropomyosin receptor kinase) family of RTKs, naturally activated by neurotrophins, with photosensory core module of DrBphP bacterial phytochrome to develop opto-kinases, termed Dr-TrkA and Dr-TrkB, reversibly switchable on and off with near-infrared and far-red light. We validated Dr-Trk ability to reversibly light-control several RTK pathways, calcium level, and demonstrated that their activation triggers canonical Trk signaling. Dr-TrkA induced apoptosis in neuroblastoma and glioblastoma, but not in other cell types. Absence of spectral crosstalk between Dr-Trks and blue-light-activatable LOV-domain-based translocation system enabled intracellular targeting of Dr-TrkA independently of its activation, additionally modulating Trk signaling. Dr-Trks have several superior characteristics that make them the opto-kinases of choice for regulation of RTK signaling: high activation range, fast and reversible photoswitching, and multiplexing with visible-light-controllable optogenetic tools. Nature Publishing Group UK 2019-03-08 /pmc/articles/PMC6408446/ /pubmed/30850602 http://dx.doi.org/10.1038/s41467-019-08988-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Leopold, Anna V.
Chernov, Konstantin G.
Shemetov, Anton A.
Verkhusha, Vladislav V.
Neurotrophin receptor tyrosine kinases regulated with near-infrared light
title Neurotrophin receptor tyrosine kinases regulated with near-infrared light
title_full Neurotrophin receptor tyrosine kinases regulated with near-infrared light
title_fullStr Neurotrophin receptor tyrosine kinases regulated with near-infrared light
title_full_unstemmed Neurotrophin receptor tyrosine kinases regulated with near-infrared light
title_short Neurotrophin receptor tyrosine kinases regulated with near-infrared light
title_sort neurotrophin receptor tyrosine kinases regulated with near-infrared light
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408446/
https://www.ncbi.nlm.nih.gov/pubmed/30850602
http://dx.doi.org/10.1038/s41467-019-08988-3
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