Optogenetic control of signaling in mammalian cells

Biotechnol J. 2015 Feb;10(2):273-83. doi: 10.1002/biot.201400077. Epub 2014 Sep 12.


Molecular signals are sensed by their respective receptors and information is transmitted and processed by a sophisticated intracellular network controlling various biological functions. Optogenetic tools allow the targeting of specific signaling nodes for a precise spatiotemporal control of downstream effects. These tools are based on photoreceptors such as phytochrome B (PhyB), cryptochrome 2, or light-oxygen-voltage-sensing domains that reversibly bind to specific interaction partners in a light-dependent manner. Fusions of a protein of interest to the photoreceptor or their interaction partners may enable the control of the protein function by light-mediated dimerization, a change of subcellular localization, or due to photocaging/-uncaging of effectors. In this review, we summarize the photoreceptors and the light-based mechanisms utilized for the modulation of signaling events in mammalian cells focusing on non-neuronal applications. We discuss in detail optogenetic tools and approaches applied to control signaling events mediated by second messengers, Rho GTPases and growth factor-triggered signaling cascades namely the RAS/RAF and phosphatidylinositol-3-kinase pathways. Applying the latest generation of optogenetic tools allows to control cell fate decisions such as proliferation and differentiation or to deliver therapeutic substances in a spatiotemporally controlled manner.

Keywords: Cryptochrome 2; Light-oxygen-voltage domains; Optogenetics; Phytochrome B; RAF/MEK/ERK pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cryptochromes / chemistry
  • Cryptochromes / metabolism
  • Humans
  • Models, Molecular
  • Optogenetics / methods*
  • Photoreceptor Cells / chemistry*
  • Photoreceptor Cells / metabolism*
  • Phytochrome B / chemistry
  • Phytochrome B / metabolism
  • Signal Transduction*


  • Cryptochromes
  • Phytochrome B