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Related Experiment Video

Updated: Feb 1, 2026

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
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Optogenetic Translocation to Subcellular Compartments through Regulation of Protein Avidity.

Zikang Dennis Huang1, Yueying Gu1, Yuzhi Carol Gao1

  • 1Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.

ACS Synthetic Biology
|January 30, 2026
PubMed
Summary

Researchers developed Avidity-assisted targeting (Aviatar), a novel single-component system for inducible protein translocation. This strategy uses inducible clustering to control protein localization within cells, simplifying complex cellular pathway manipulation.

Keywords:
avidityoptogeneticssubcellular localizationtranslocation, RTK fusions

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biotechnology

Background:

  • Inducible protein translocation to specific subcellular compartments is crucial for regulating cellular behaviors.
  • Existing methods often rely on induced dimerization, requiring two components and complex optimization.
  • These limitations necessitate simpler, more adaptable strategies for controlling protein localization.

Purpose of the Study:

  • To introduce and validate Avidity-assisted targeting (Aviatar), a novel single-component system for inducible protein translocation.
  • To demonstrate the versatility of Aviatar across various subcellular compartments.
  • To showcase Aviatar's utility in regulating cellular processes and signaling pathways.

Main Methods:

  • Developed Aviatar, a single-component strategy converting low-affinity monomers into high-avidity assemblies via inducible clustering.
  • Utilized optogenetic clustering to drive Aviatar-mediated translocation to diverse compartments (plasma membrane, endosomes, Golgi, ER, microtubules).
  • Employed compartment-specific binding domains for lipids or endogenous proteins.

Main Results:

  • Successfully demonstrated Aviatar-driven translocation to multiple subcellular locations.
  • Showcased Aviatar's ability to regulate actin polymerization and reveal compartment-specific signaling of receptor tyrosine kinase fusions.
  • Developed GFP-targeting Aviatar probes for inducible localization to GFP-tagged proteins, including stress granule proteins.

Conclusions:

  • Aviatar offers a simplified, single-component approach to inducible protein translocation.
  • The platform is versatile and can be rapidly adapted to various cellular targets without prior modification.
  • Aviatar provides a powerful tool for dissecting cellular functions and signaling pathways.