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Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
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Related Experiment Video

Updated: Aug 24, 2025

Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes
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Imaging and Editing the Phospholipidome.

Din-Chi Chiu1,2, Jeremy M Baskin1,2

  • 1Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States.

Accounts of Chemical Research
|October 24, 2022
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Summary
This summary is machine-generated.

Researchers developed chemical tools to image and edit cellular phospholipids, revealing new insights into cell signaling and organelle function. These methods, including bioorthogonal chemistry and optogenetics, advance our understanding of lipid biology.

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Area of Science:

  • Cell Biology
  • Chemical Biology
  • Biochemistry

Background:

  • Cellular membranes, primarily composed of glycerophospholipids, are crucial for cell structure and function.
  • Organelle-specific phospholipid compositions are vital for cellular processes, regulated by complex lipid-metabolizing enzymes and transporters.
  • Chemical approaches offer precision tools to visualize, manipulate, and understand lipid roles in cells.

Purpose of the Study:

  • To develop and apply chemical strategies for imaging and editing the cellular phospholipidome.
  • To investigate the roles of specific phospholipid pathways, particularly phospholipase D (PLD) signaling and phosphatidic acid (PA) production.
  • To create novel tools for visualizing lipid localization, abundance, and interactions within cells.

Main Methods:

  • Utilized bioorthogonal chemistry, including IMPACT (In-situ imaging and manipulation by bioorthogonal chemistry) methods, for fluorescent lipid reporters.
  • Employed tetrazine ligation for spatiotemporal dynamics studies and diazirine photo-cross-linkers for lipid-protein interaction analysis.
  • Developed optogenetic and enzyme-evolved PLD tools for precise membrane phospholipid editing and PA synthesis.

Main Results:

  • IMPACT methods revealed dynamics of GPCR signaling, interorganelle lipid transport, and identified lipid-protein interactions linked to alcohol-related diseases.
  • CRISPR screening combined with IMPACT identified genes regulating PLD signaling.
  • Optogenetic PLD and engineered superPLDs demonstrated control over organelle PA levels and phospholipid composition, impacting Hippo signaling.

Conclusions:

  • Developed versatile chemical tools for imaging and editing the phospholipidome, advancing lipid biology.
  • Demonstrated the utility of these tools in uncovering roles of specific lipids in cell signaling and organelle function.
  • Highlighted future directions for extending these chemical strategies to other lipid classes and uncovering new regulatory mechanisms.