Quantitative control of subcellular protein localization with a photochromic dimerizer

Area of Science:

• Cell Biology
• Biochemistry
• Molecular Imaging

Background:

• Optogenetics and chemically induced dimerization (CID) systems offer spatiotemporal control of intracellular protein dynamics.
• Existing methods face limitations in controlling activation duration, deactivation rates, and repetitive cycles.

Purpose of the Study:

• To develop a photochromic CID system for precise, light-driven regulation of intracellular protein dynamics.
• To enable rapid, repetitive, and quantitative control over protein localization using light.

Main Methods:

• Utilized photoisomerization of a ligand to achieve light-controlled association and dissociation in a CID system.
• Demonstrated the system's application in multicolor fluorescence imaging for studying cellular processes.
• Applied the system to investigate PTEN-induced kinase 1 (PINK1)-Parkin-mediated mitophagy.

Main Results:

• Achieved quick, repetitive, and quantitative regulation of target protein localization via violet and green light illumination.
• Successfully manipulated PINK1-Parkin-mediated mitophagy, demonstrating light-controlled protein recruitment.
• Showcased the system's utility in finely manipulating intracellular protein dynamics during multicolor imaging.

Conclusions:

• The developed photochromic CID system offers advanced control over intracellular protein dynamics.
• This system provides a valuable tool for studying complex cellular processes, including mitophagy.
• Light-based control enhances the precision and versatility of studying biomolecular networks.