Direct multiplex imaging and optogenetics of Rho GTPases enabled by near-infrared FRET

Nat Chem Biol. 2018 Jun;14(6):591-600. doi: 10.1038/s41589-018-0044-1. Epub 2018 Apr 23.

Abstract

Direct visualization and light control of several cellular processes is a challenge, owing to the spectral overlap of available genetically encoded probes. Here we report the most red-shifted monomeric near-infrared (NIR) fluorescent protein, miRFP720, and the fully NIR Förster resonance energy transfer (FRET) pair miRFP670-miRFP720, which together enabled design of biosensors compatible with CFP-YFP imaging and blue-green optogenetic tools. We developed a NIR biosensor for Rac1 GTPase and demonstrated its use in multiplexed imaging and light control of Rho GTPase signaling pathways. Specifically, we combined the Rac1 biosensor with CFP-YFP FRET biosensors for RhoA and for Rac1-GDI binding, and concurrently used the LOV-TRAP tool for upstream Rac1 activation. We directly observed and quantified antagonism between RhoA and Rac1 dependent on the RhoA-downstream effector ROCK; showed that Rac1 activity and GDI binding closely depend on the spatiotemporal coordination between these two molecules; and simultaneously observed Rac1 activity during optogenetic manipulation of Rac1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biosensing Techniques
  • Bradyrhizobium
  • Fluorescence Resonance Energy Transfer*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Optogenetics
  • Plasmids
  • Protein Binding
  • Signal Transduction
  • Spectroscopy, Near-Infrared
  • cdc42 GTP-Binding Protein / chemistry
  • rac1 GTP-Binding Protein / chemistry
  • rho GTP-Binding Proteins / chemistry*

Substances

  • RAC1 protein, human
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein
  • rho GTP-Binding Proteins