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Optical control of sphingolipid biosynthesis using photoswitchable sphingosines
Matthijs Kol1,2, Alexander J E Novak3, Johannes Morstein4
1Molecular Cell Biology Division, Department of Biology/Chemistry, Osnabrück University, 49076 Osnabrück, Germany.
Biorxiv : the Preprint Server for Biology
|November 1, 2024
Summary
Researchers developed light-sensitive sphingolipids (caSph) to control sphingolipid biosynthesis. These molecules allow precise, reversible manipulation of cellular lipid production using light, offering new research tools.
Area of Science:
- Biochemistry
- Cell Biology
- Chemical Biology
Background:
- Sphingolipid metabolism is a complex network crucial for cellular processes.
- Understanding this network is difficult due to short-lived intermediates with opposing activities.
Purpose of the Study:
- To develop novel tools for precise control over sphingolipid biosynthesis.
- To investigate the impact of light-induced structural changes on sphingolipid metabolism.
Main Methods:
- Introduction of clickable, azobenzene-containing sphingosines (caSph) as light-sensitive substrates.
- Utilizing photo-isomerization to switch caSph between trans and cis forms.
- Employing in vitro enzyme assays and metabolic labeling studies in living cells.
Main Results:
- Trans-to-cis isomerization of caSph significantly stimulates conversion by ceramide and sphingomyelin synthases.
- Light-induced changes in sphingolipid production are rapid, reversible, and efficient in cells.
- caSph enables spatiotemporal control over sphingolipid biosynthesis.
Conclusions:
- caSph are versatile tools for manipulating sphingolipid biosynthesis with light.
- This technology opens new avenues for studying sphingolipid function and regulation.
