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New Biological Frontiers Illuminated by Molecular Sensors and Actuators
Poster Abstracts
21-POS
Board 21
Optogenetic Toolkit for Regulation of Receptor Tyrosine Kinases Signaling
Minji Lee
1
, Nury Kim
2
, Jin Man Kim
1
, Doyeon Woo
1
, Wondo Heo
1,2
.
1
KAIST, Daejeon, South Korea,
2
Institute for Basic Science (IBS), Daejeon, South Korea.
Receptor tyrosine kinases (RTKs) are a family of cell-surface receptors which mediate cell
migration, proliferation, differentiation and angiogenesis in various cells and tissues.
In Arabidopsis thaliana, cryptochrome is blue light photoreceptor that includes a N-terminal
photolyase homology region (PHR) that mediates light-responsive dimerization through binding
to chromophores and C-terminal extension domain that involved in signaling transduction by
interacting other partner. Homo-oligomerization of cryptochrome 2 is mediated through the PHR
domain. PHR of Cryptochrome 2 (CRY2PHR) fused controlling system to receptor tyrosine
kinases using CRY2PHR oligomerization promises a powerful tool to study cell signaling
because of its fast responsiveness with subsecond time resolution, spatial resolution, reversibility
and no need for exogenous cofactors.
Here, we engineered optically controlled RTKs (optoRTKs) by exploiting cryptochrome 2,
which homointeracts upon blue light irradiation. After screening, we found out that fibroblast
growth factor receptor (FGFR) and tropomyosin receptor kinase (Trk) can be activated by blue
light-induced homointeraction of CRY2PHR. The major downstream signaling pathways of
RTKs, canonical signals can activated by light stimulation with precise, rapid and reversible
manner. The genetically modified light-inducible RTKs, optoRTKs, shed us a potential on the
study of receptor tyrosine kinases signaling in various biological systems.