Aptamer-based optical manipulation of protein subcellular localization in cells

Area of Science:

• Biotechnology
• Molecular Biology
• Cellular Biology

Background:

• Precise control over protein activity and localization is crucial for understanding cellular processes.
• Optogenetic methods offer spatiotemporal control but often require genetic modification via fusion proteins, potentially causing artifacts.
• Existing techniques lack methods to manipulate native proteins without altering their structure or function.

Purpose of the Study:

• To develop a novel aptamer-based nanoplatform for light-inducible manipulation of native protein subcellular localization.
• To demonstrate photocontrol over protein shuttling and downstream signaling pathways.
• To create a versatile platform for studying various proteins and biological events.

Main Methods:

• Design of a tunable aptamer-based recognition unit.
• Development of a near-infrared (NIR) light-responsive nanoplatform.
• Application of the nanoplatform for photocontrol of RelA protein (NF-κβ family) cytoplasmic-nuclear shuttling.
• Demonstration of modularity for targeting other proteins like lysozyme and p53.

Main Results:

• The aptamer-based nanoplatform successfully achieved spatiotemporal photocontrol over protein localization.
• Demonstrated precise regulation of the cytoplasmic-nuclear shuttling of the target RelA protein.
• Enabled modulation of RelA-related signaling pathways through light-induced localization changes.
• Showcased the platform's modularity and potential for targeting diverse proteins.

Conclusions:

• The developed aptamer-based nanoplatform provides a powerful tool for label-free, light-controlled manipulation of native protein localization.
• This technology offers a new strategy for studying complex biological events and signaling pathways.
• The modular design holds significant potential for broad applications in proteomics and cell biology research.