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bioRxiv · 10.1101/2024.03.26.586876

A Hollow TFG Condensate Spatially Compartmentalizes the Early Secretory Pathway

Wegeng, W. R.·Bogus, S. M.·Ruiz, M.·Chavez, S. R.·Noori, K. S. M.·Niesman, I. R.·Ernst, A. M.
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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, Trk-fused gene (TFG) self-organizes to form a hollow, anisotropic condensate that matches the dimensions of the ER-Golgi interface. 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, enabling molecules corresponding to the size of anterograde coats (COPII) to access 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 bidirectional transport. We further propose that TFG condensates optimize membrane flux by insulating secretory carriers in their lumen from retrograde carriers outside TFG cages.

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Wegeng, W. R., Bogus, S. M., Ruiz, M., Chavez, S. R., Noori, K. S. M., Niesman, I. R., Ernst, A. M.. 2024-03-27. A Hollow TFG Condensate Spatially Compartmentalizes the Early Secretory Pathway. https://doi.org/10.1101/2024.03.26.586876

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