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Protease-controlled secretion and display of intercellular signals
Alexander E Vlahos1, Jeewoo Kang2, Carlos A Aldrete1
1Department of Chemical Engineering, Stanford University, Stanford, CA, 94305, USA.
Nature Communications
|February 18, 2022
Summary
We developed Retained Endoplasmic Cleavable Secretion (RELEASE) to control protein display and secretion. This programmable system enables precise intercellular communication for biomedical applications.
Area of Science:
- Biotechnology
- Molecular Biology
- Synthetic Biology
Background:
- Regulating intercellular communication is vital for biomedicine.
- Protein-level control offers advantages like compact delivery and direct pathway interaction.
Purpose of the Study:
- To create a modular and generalizable system for programmable protein secretion and surface display.
- To enable precise control over intercellular signaling for biomedical applications.
Main Methods:
- Developed the Retained Endoplasmic Cleavable Secretion (RELEASE) system.
- Engineered proteins retained in the endoplasmic reticulum, released by specific proteases.
- Integrated RELEASE with synthetic protease circuits for signal processing.
Main Results:
- Demonstrated functional regulation of synthetic and natural proteins.
- Achieved signal processing capabilities, including logic operations and threshold tuning.
- Enabled elevated protein secretion in response to KRAS mutants by linking RELEASE to sensing circuits.
Conclusions:
- RELEASE provides a programmable platform for controlling protein secretion and display.
- This technology facilitates localized delivery of intercellular cues for diverse fields.
- Applications include neurobiology, cancer immunotherapy, and cell transplantation.
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