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FRET Microscopy for Real-time Monitoring of Signaling Events in Live Cells Using Unimolecular Biosensors
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FRET Microscopy for Real-time Monitoring of Signaling Events in Live Cells Using Unimolecular Biosensors

Published on: August 20, 2012

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Shedding new light on RhoA signalling as a drug target in vivo using a novel RhoA-FRET biosensor mouse

Max Nobis1, David Herrmann1, Sean C Warren1

  • 1The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, University of New South Wales , Sydney, 2010 NSW, Australia.

Small Gtpases
|February 20, 2018
PubMed

Insights

Researchers developed a novel RhoA-FRET biosensor mouse to study RhoA signaling in vivo. This tool enables real-time observation of RhoA activity in various physiological and pathological conditions, aiding in the development of new cancer therapies.

Area of Science:

  • Cellular signaling and mechanotransduction
  • Cancer biology and therapeutics
  • In vivo imaging and biosensing

Background:

  • The small GTPase RhoA is a key regulator of cell-extracellular matrix interactions, crucial for processes like migration and mechanotransduction.
  • Dysregulated RhoA signaling is implicated in carcinogenesis, but studying its activity in native tissues is challenging with conventional methods.
  • Intravital imaging offers a promising approach for real-time analysis of cellular signaling within living organisms.

Purpose of the Study:

  • To develop and validate a RhoA-FRET biosensor mouse for investigating RhoA activity in vivo.
  • To utilize this tool to explore RhoA signaling dynamics in diverse physiological and pathological contexts.
  • To enable temporal resolution of pharmacological interventions targeting RhoA signaling in vivo.

Main Methods:

  • Development of a genetically engineered mouse model expressing a RhoA-Förster Resonance Energy Transfer (FRET) biosensor.
  • Application of intravital imaging techniques to visualize RhoA activity in various tissues and conditions.
  • Analysis of RhoA signaling during mechanotransduction, neutrophil migration, tissue remodeling, and carcinogenesis.

Main Results:

  • Demonstrated RhoA-FRET mouse's capability to visualize RhoA activity in osteocyte mechanotransduction, neutrophil chemotaxis, and mammary gland remodeling.
  • Observed tightly regulated RhoA activity during mammary and pancreatic carcinogenesis.
  • Successfully resolved the temporal effects of RhoA inhibition in established mammary and pancreatic tumors in vivo.

Conclusions:

  • The RhoA-FRET biosensor mouse is a powerful tool for studying RhoA signaling in native tissue environments.
  • This model facilitates real-time investigation of RhoA's role in diverse biological processes and diseases.
  • The developed tool can accelerate the discovery and development of novel therapeutic inhibitors targeting the RhoA signaling axis.
Keywords:
FLIMFRETIntravital imagingRho-GTPasesRhoAbiosensorsbreast cancerextracellular matrixpancreatic cancer

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