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Spatiotemporal control of subcellular O-GlcNAc signaling using Opto-OGT
Qunxiang Ong1,2, Ler Ting Rachel Lim1, Cameron Goh1
1Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Nature Chemical Biology
|November 15, 2024
Summary
Researchers developed Opto-OGT, a light-activated tool to control O-linked β-N-acetylglucosamine (O-GlcNAc) modification. This probe precisely manipulates O-GlcNAc transferase (OGT) activity, offering new insights into cellular signaling and physiology.
Area of Science:
- Cellular Biology
- Biochemistry
- Molecular Biology
Background:
- O-linked β-N-acetylglucosamine (O-GlcNAc) is a crucial post-translational modification regulating diverse cellular processes.
- O-GlcNAc transferase (OGT) catalyzes this modification, impacting signal transduction, gene expression, and overall physiology.
Purpose of the Study:
- To develop a novel optogenetic tool, Opto-OGT, for precise spatiotemporal control over OGT activity.
- To investigate the role of O-GlcNAcylation in nutrient-sensing pathways and insulin signaling.
Main Methods:
- Engineered Opto-OGT by fusing OGT with a photosensitive cryptochrome protein.
- Utilized blue light to activate and reversibly control Opto-OGT activity with high temporal resolution.
- Targeted Opto-OGT to specific subcellular locations, such as the plasma membrane.
Main Results:
- Opto-OGT activation mimicked nutrient-sensing signaling by inducing mTORC activation and AMPK suppression.
- Subcellular targeting of Opto-OGT demonstrated its ability to modulate site-specific AKT phosphorylation.
- Light-induced OGT activity led to altered insulin signaling outputs.
Conclusions:
- Opto-OGT provides a powerful and precise method for studying O-GlcNAcylation dynamics in living cells.
- This tool enables detailed investigation into the physiological roles of O-GlcNAcylation in various signaling pathways.
- Opto-OGT facilitates a deeper understanding of how O-GlcNAcylation impacts cellular functions and systemic physiology.
