Biophysical Society Thematic Meeting - June 28-July 1, 2015

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.

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