A hollow TFG condensate spatially compartmentalizes the early secretory pathway

Savannah M. Bogus, William R. Wegeng, Miguel Ruiz, Sindy R. Chavez, Samantha N. Cheung, Khalid S. M. Noori, Ingrid R. Niesman and Andreas M. Ernst ()
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Savannah M. Bogus: University of California San Diego
William R. Wegeng: University of California San Diego
Miguel Ruiz: University of California San Diego
Sindy R. Chavez: University of California San Diego
Samantha N. Cheung: University of California San Diego
Khalid S. M. Noori: University of California San Diego
Ingrid R. Niesman: San Diego State University
Andreas M. Ernst: University of California San Diego

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract In the early secretory pathway, endoplasmic reticulum (ER) and Golgi membranes form a nearly spherical interface. In this ribosome-excluding zone, bidirectional transport of cargo coincides with a spatial segregation of anterograde and retrograde carriers by an unknown mechanism. We show that at physiological conditions, the Trk-fused gene (TFG) self-organizes to form a hollow, anisotropic condensate that matches the dimensions of the ER–Golgi interface and is dynamically regulated across the cell cycle. Regularly spaced hydrophobic residues in TFG control the condensation mechanism and result in a porous condensate surface. We find that TFG condensates act as a molecular sieve capable of allowing access of anterograde coats (COPII) to the condensate interior while restricting retrograde coats (COPI). We propose that a hollow TFG condensate structures the ER–Golgi interface to create a diffusion-limited space for anterograde transport. We further propose that TFG condensates optimize membrane flux by insulating secretory carriers in their lumen from retrograde carriers outside TFG cages.

Date: 2025
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DOI: 10.1038/s41467-025-59118-1

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