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Endosome motility defects revealed at super-resolution in live cells using HIDE probes
Aarushi Gupta1, Felix Rivera-Molina2, Zhiqun Xi2
1Department of Chemistry, Yale University, New Haven, CT, USA.
Nature Chemical Biology
|February 26, 2020
Summary
Researchers developed new lipid-based probes to visualize endo-lysosome dynamics using super-resolution microscopy. These probes reveal organelle defects and rare kiss-and-run events, advancing our understanding of cellular transport.
Area of Science:
- Cell Biology
- Biochemistry
- Microscopy
Background:
- Endo-lysosomes are crucial for cellular waste disposal and nutrient recycling.
- Tracking endo-lysosome dynamics is vital for understanding cellular health and disease.
- Existing imaging techniques have limitations in visualizing dynamic organelle processes.
Purpose of the Study:
- To develop novel probes for high-resolution, long-term imaging of endo-lysosome dynamics.
- To investigate endosome motility defects in Niemann-Pick Type-C disease.
- To uncover novel endosomal transport mechanisms.
Main Methods:
- Synthesis of lipid-based, high-density, environmentally sensitive (HIDE) probes (DiIC16-SiR and DiIC16'-SiR) via tetrazine ligation.
- Super-resolution microscopy for live-cell imaging of organelle dynamics.
- Analysis of endosome structure, function, and motility in wild-type and patient-derived cells.
Main Results:
- HIDE probes enable over 7-minute super-resolution imaging of endo-lysosomes without affecting cell viability.
- Demonstrated endosome motility defects in Niemann-Pick Type-C disease patient cells.
- Observed rare 'kiss-and-run' events between endosomes in wild-type cells, previously undetectable.
Conclusions:
- HIDE probes are effective tools for studying endo-lysosome biology and dynamics.
- The findings provide insights into NPC1's role in organelle motility and cholesterol trafficking.
- This research opens new avenues for diagnosing and understanding lysosomal storage disorders.
