Stress-induced phase separation of ERES components into Sec bodies precedes ER exit inhibition in mammalian cells
| Autor: | van Leeuwen, Wessel, Nguyen, Dan T M, Grond, Rianne, Veenendaal, Tineke, Rabouille, Catherine, Farías, Ginny G, Celbiologie, Sub Cell Biology |
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| Přispěvatelé: | Hubrecht Institute for Developmental Biology and Stem Cell Research, Celbiologie, Sub Cell Biology |
| Rok vydání: | 2022 |
| Předmět: |
Mammals
Golgi Apparatus/metabolism Sec16 Secretory Pathway Protein transport Mammals/metabolism ERES remodeling Phase separation Vesicular Transport Proteins Mammalian cells Golgi Apparatus Cell Biology Stress Endoplasmic Reticulum Vesicular Transport Proteins/genetics Protein Transport Sec body Animals COP-Coated Vesicles/metabolism Early secretory pathway COP-Coated Vesicles ER exit sites Endoplasmic Reticulum/metabolism |
| Zdroj: | Journal of Cell Science, 135(23). Company of Biologists Ltd Journal of Cell Science, 135(23). COMPANY OF BIOLOGISTS LTD |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | Phase separation of ER-exit-sites (ERES) components into membraneless compartments, the Sec bodies, occurs in Drosophila cells upon specific cellular stressors, i.e., salt stress and amino acid starvation, and their formation is linked to the inhibition of the early secretory pathway. Here, we show Sec bodies also form in secretory mammalian INS-1 cells upon the same stress. These reversible and membraneless structures are positive for ERES components, including both isoforms of Sec16 (A and B) and COPII subunits. We find that Sec16A, but not Sec16B, is a driver for Sec body formation. We show that the coalescence of ERES components into Sec bodies occurs by fusion, in line with their liquid-droplet properties. Lastly, we demonstrate that stress-induced ER-exit inhibition is a consequence of the significant coalescence of Sec16A into Sec bodies, leading to its depletion from ERES that become non-functional. Stress relief causes an immediate dissolution of Sec bodies and the concomitant restoration of protein exit from the ER. We propose a model in which dynamic conversion between ERES and Sec body assembly, driven by Sec16A, regulates protein exit from the ER during stress and upon stress relief in mammalian cells, thus providing a conserved pro-survival mechanism in response to stress. |
| Databáze: | OpenAIRE |
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