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Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
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Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Published on: October 4, 2024

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Control of SRC molecular dynamics encodes distinct cytoskeletal responses by specifying signaling pathway usage

Adèle Kerjouan1, Cyril Boyault1, Christiane Oddou1

  • 1Institute for Advanced Biosciences, Centre de Recherche Université Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, 38706 La Tronche, France.

Journal of Cell Science
|January 26, 2021
PubMed

Insights

Scientists developed optogenetic probes to control SRC signaling, revealing how molecular mobility dictates distinct cellular responses like lamellipodia or invadosomes. This work uncovers the pleiotropy-encoding mechanism of SRC signaling.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Biophysics

Background:

  • Single signaling proteins can trigger diverse cellular outcomes.
  • Understanding the mechanisms behind this pleiotropic signaling is crucial.
  • Directly manipulating cellular decision-making processes offers insight.

Purpose of the Study:

  • To develop a tool for controlling SRC signaling dynamics.
  • To investigate how spatio-temporal control of SRC activity influences cellular responses.
  • To elucidate the pleiotropy-encoding mechanism of SRC signaling.

Main Methods:

  • Development of an optogenetic probe (optoSRC) to control SRC kinase activity.
  • Distinct spatio-temporal control of optoSRC nanocluster dynamics at adhesive sites.
  • Time-resolved proteomic and network analyses to characterize downstream signaling pathways.

Main Results:

  • OptoSRC successfully generated distinct acto-adhesive structures (lamellipodia or invadosomes).
  • Cellular response was dictated by the dynamics of optoSRC nanoclusters, dependent on SH3 and Unique domains.
  • Distinct downstream signaling pathways were induced by different optoSRC dynamics.

Conclusions:

  • Molecular mobility of SRC kinase activity is a key determinant of pleiotropy.
  • The SH3 and Unique domains are critical for regulating optoSRC nanocluster dynamics and cellular decisions.
  • This study provides a novel approach to dissecting complex signaling networks.
Keywords:
AdhesionsConformational intermediatesCytoskeletalEncoding intracellular signalingInvasionMigrationOptogeneticsPleiotropySRCTime-resolved phosphoproteomics

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