A hollow TFG condensate spatially compartmentalizes the early secretory pathway
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 th...
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| Format: | Article |
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59118-1 |
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| author | Savannah M. Bogus William R. Wegeng Miguel Ruiz Sindy R. Chavez Samantha N. Cheung Khalid S. M. Noori Ingrid R. Niesman Andreas M. Ernst |
| author_facet | Savannah M. Bogus William R. Wegeng Miguel Ruiz Sindy R. Chavez Samantha N. Cheung Khalid S. M. Noori Ingrid R. Niesman Andreas M. Ernst |
| author_sort | Savannah M. Bogus |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6f104f51b38f44628592fa11709c9d22 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-6f104f51b38f44628592fa11709c9d222025-08-20T03:18:28ZengNature PortfolioNature Communications2041-17232025-04-0116111510.1038/s41467-025-59118-1A hollow TFG condensate spatially compartmentalizes the early secretory pathwaySavannah M. Bogus0William R. Wegeng1Miguel Ruiz2Sindy R. Chavez3Samantha N. Cheung4Khalid S. M. Noori5Ingrid R. Niesman6Andreas M. Ernst7Department of Cell and Developmental Biology, School of Biological Sciences, University of California San DiegoDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California San DiegoDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California San DiegoDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California San DiegoDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California San DiegoDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California San DiegoDepartment of Biology, San Diego State UniversityDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California San DiegoAbstract 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.https://doi.org/10.1038/s41467-025-59118-1 |
| spellingShingle | Savannah M. Bogus William R. Wegeng Miguel Ruiz Sindy R. Chavez Samantha N. Cheung Khalid S. M. Noori Ingrid R. Niesman Andreas M. Ernst A hollow TFG condensate spatially compartmentalizes the early secretory pathway Nature Communications |
| title | A hollow TFG condensate spatially compartmentalizes the early secretory pathway |
| title_full | A hollow TFG condensate spatially compartmentalizes the early secretory pathway |
| title_fullStr | A hollow TFG condensate spatially compartmentalizes the early secretory pathway |
| title_full_unstemmed | A hollow TFG condensate spatially compartmentalizes the early secretory pathway |
| title_short | A hollow TFG condensate spatially compartmentalizes the early secretory pathway |
| title_sort | hollow tfg condensate spatially compartmentalizes the early secretory pathway |
| url | https://doi.org/10.1038/s41467-025-59118-1 |
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