Light-inducible Receptor Tyrosine Kinases That Regulate Neurotrophin Signalling

Nat Commun. 2014 Jun 4;5:4057. doi: 10.1038/ncomms5057.

Abstract

Receptor tyrosine kinases (RTKs) are a family of cell-surface receptors that have a key role in regulating critical cellular processes. Here, to understand and precisely control RTK signalling, we report the development of a genetically encoded, photoactivatable Trk (tropomyosin-related kinase) family of RTKs using a light-responsive module based on Arabidopsis thaliana cryptochrome 2. Blue-light stimulation (488 nm) of mammalian cells harbouring these receptors robustly upregulates canonical Trk signalling. A single light stimulus triggers transient signalling activation, which is reversibly tuned by repetitive delivery of blue-light pulses. In addition, the light-provoked process is induced in a spatially restricted and cell-specific manner. A prolonged patterned illumination causes sustained activation of extracellular signal-regulated kinase and promotes neurite outgrowth in a neuronal cell line, and induces filopodia formation in rat hippocampal neurons. These light-controllable receptors are expected to create experimental opportunities to spatiotemporally manipulate many biological processes both in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arabidopsis
  • Arabidopsis Proteins / genetics
  • Cell Line
  • Cryptochromes / genetics
  • Hippocampus / cytology
  • Humans
  • Light
  • Nerve Growth Factors / metabolism*
  • Neurites / metabolism*
  • Neurons / metabolism*
  • Pseudopodia / metabolism*
  • Rats
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, trkA / metabolism
  • Receptor, trkB / metabolism
  • Receptor, trkC / metabolism

Substances

  • Arabidopsis Proteins
  • Cryptochromes
  • Nerve Growth Factors
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA
  • Receptor, trkB
  • Receptor, trkC