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Neurotrophin receptor tyrosine kinases regulated with near-infrared light
- Source :
- Nature Communications, Vol 10, Iss 1, Pp 1-13 (2019), Nature Communications
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
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.<br />Optical control over receptor tyrosine kinase (RTK) activity can find application in both basic biology and synthetic biology. Here the authors combine the photosensory module of DrBphP bacterial phytochrome with the Trk family of RTKs to obtain Trks that are reversibly switchable with near-infrared and far-red light.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
General Physics and Astronomy
Apoptosis
02 engineering and technology
Tropomyosin receptor kinase A
Protein Engineering
Receptor tyrosine kinase
ACTIVATION
Mice
Receptor
lcsh:Science
Neurons
Multidisciplinary
biology
TRKA
Chemistry
Kinase
021001 nanoscience & nanotechnology
Cell biology
FLUORESCENT PROTEINS
ERK
Crosstalk (biology)
embryonic structures
Phytochrome
0210 nano-technology
Neuroglia
Neurotrophin
Light Signal Transduction
animal structures
Infrared Rays
Science
Recombinant Fusion Proteins
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Bacterial Proteins
Cell Line, Tumor
Animals
Humans
Receptor, trkB
Nerve Growth Factors
Receptor, trkA
TOOLS
fungi
Epithelial Cells
General Chemistry
Optogenetics
030104 developmental biology
Gene Expression Regulation
CELL-DEATH
nervous system
Trk receptor
biology.protein
lcsh:Q
BIOSENSORS
3111 Biomedicine
HeLa Cells
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....1ec317c63bd687a798a2d030984fdbce