Neurotrophin receptor tyrosine kinases regulated with near-infrared light

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Leopold , A V , Chernov , K G , Shemetov , A A & Verkhusha , V V 2019 , ' Neurotrophin receptor tyrosine kinases regulated with near-infrared light ' , Nature Communications , vol. 10 , 1129 .

Title: Neurotrophin receptor tyrosine kinases regulated with near-infrared light
Author: Leopold, Anna V.; Chernov, Konstantin G.; Shemetov, Anton A.; Verkhusha, Vladislav V.
Contributor organization: Department of Anatomy
University of Helsinki
Date: 2019-03-08
Language: eng
Number of pages: 13
Belongs to series: Nature Communications
ISSN: 2041-1723
Abstract: 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.
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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