Neurotrophin receptor tyrosine kinases regulated with near-infrared light

Anna V. Leopold, Konstantin G. Chernov, Anton Shemetov, Vladislav Verkhusha

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Article number1129
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

Nerve Growth Factor Receptors
tyrosine
Receptor Protein-Tyrosine Kinases
Protein-Tyrosine Kinases
Tropomyosin
Phosphotransferases
Infrared radiation
Light
Chemical activation
Optogenetics
Phytochrome
Nerve Growth Factors
activation
Glioblastoma
Neuroblastoma
Catalytic Domain
phytochrome
Apoptosis
Crosstalk
Calcium

ASJC Scopus subject areas

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

Cite this

Neurotrophin receptor tyrosine kinases regulated with near-infrared light. / Leopold, Anna V.; Chernov, Konstantin G.; Shemetov, Anton; Verkhusha, Vladislav.

In: Nature Communications, Vol. 10, No. 1, 1129, 01.12.2019.

Research output: Contribution to journalArticle

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