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A Hollow TFG Condensate Spatially Compartmentalizes the Early Secretory Pathway
William R Wegeng1, Savannah M Bogus1, Miguel Ruiz1
1Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA 92093 USA.
Biorxiv : the Preprint Server for Biology
|April 8, 2024
Summary
Trk-fused gene (TFG) self-organizes into hollow condensates, acting as a molecular sieve. This structure at the ER-Golgi interface spatially separates transport carriers, optimizing cellular membrane flux.
Area of Science:
- Cell biology
- Molecular mechanisms of intracellular transport
- Biophysics of protein self-assembly
Background:
- The early secretory pathway involves transport between the endoplasmic reticulum (ER) and Golgi apparatus.
- Bidirectional cargo transport occurs at the ER-Golgi interface, a ribosome-excluding zone.
- The mechanism for spatial segregation of anterograde and retrograde carriers is unknown.
Purpose of the Study:
- To investigate the role of Trk-fused gene (TFG) in organizing the ER-Golgi interface.
- To elucidate the mechanism by which TFG spatially segregates transport carriers.
- To understand how TFG influences membrane flux in the secretory pathway.
Main Methods:
- In vitro self-assembly studies of TFG protein.
- Analysis of TFG condensate structure and porosity.
- Investigating the interaction of TFG condensates with COPII and COPI coat proteins.
- Cellular imaging to observe TFG localization and function.
Main Results:
- TFG self-organizes into hollow, anisotropic condensates at physiological conditions.
- The dimensions of TFG condensates match the ER-Golgi interface.
- Regularly spaced hydrophobic residues in TFG control condensation and create a porous surface.
- TFG condensates function as a molecular sieve, allowing COPII but not COPI access.
Conclusions:
- Hollow TFG condensates structure the ER-Golgi interface, creating a diffusion-limited space.
- TFG condensates facilitate bidirectional transport by spatially segregating carriers.
- TFG condensates optimize membrane flux by insulating secretory carriers from retrograde machinery.
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