Stress-induced phase separation of ERES components into Sec bodies precedes ER exit inhibition in mammalian cells

Wessel van Leeuwen; Dan T M Nguyen; Rianne Grond; Tineke Veenendaal; Catherine Rabouille; Ginny G Farías

doi:10.1242/jcs.260294

Stress-induced phase separation of ERES components into Sec bodies precedes ER exit inhibition in mammalian cells

Wessel van Leeuwen, Dan T M Nguyen, Rianne Grond, Tineke Veenendaal, Catherine Rabouille, Ginny G Farías

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

14 Citaten (Scopus)

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Phase separation of components of ER exit sites (ERES) into membraneless compartments, the Sec bodies, occurs in Drosophila cells upon exposure to specific cellular stressors, namely, salt stress and amino acid starvation, and their formation is linked to the early secretory pathway inhibition. Here, we show Sec bodies also form in secretory mammalian cells upon the same stress. These reversible and membraneless structures are positive for ERES components, including both Sec16A and Sec16B isoforms and COPII subunits. We find that Sec16A, but not Sec16B, is a driver for Sec body formation, and that the coalescence of ERES components into Sec bodies occurs by fusion. Finally, we show that the stress-induced coalescence of ERES components into Sec bodies precedes ER exit inhibition, leading to their progressive depletion from ERES that become non-functional. Stress relief causes an immediate dissolution of Sec bodies and the concomitant restoration of ER exit. We propose that the 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.

Originele taal-2	Engels
Tijdschrift	Journal of Cell Science
Volume	135
Nummer van het tijdschrift	23
DOI's	https://doi.org/10.1242/jcs.260294
Status	Gepubliceerd - 01 dec. 2022

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@article{f2364d7e6ddb4d9888bac4ce51905812,

title = "Stress-induced phase separation of ERES components into Sec bodies precedes ER exit inhibition in mammalian cells",

abstract = "Phase separation of components of ER exit sites (ERES) into membraneless compartments, the Sec bodies, occurs in Drosophila cells upon exposure to specific cellular stressors, namely, salt stress and amino acid starvation, and their formation is linked to the early secretory pathway inhibition. Here, we show Sec bodies also form in secretory mammalian cells upon the same stress. These reversible and membraneless structures are positive for ERES components, including both Sec16A and Sec16B isoforms and COPII subunits. We find that Sec16A, but not Sec16B, is a driver for Sec body formation, and that the coalescence of ERES components into Sec bodies occurs by fusion. Finally, we show that the stress-induced coalescence of ERES components into Sec bodies precedes ER exit inhibition, leading to their progressive depletion from ERES that become non-functional. Stress relief causes an immediate dissolution of Sec bodies and the concomitant restoration of ER exit. We propose that the 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.",

keywords = "Animals, Endoplasmic Reticulum/metabolism, COP-Coated Vesicles/metabolism, Golgi Apparatus/metabolism, Vesicular Transport Proteins/genetics, Secretory Pathway, Protein Transport, Mammals/metabolism",

author = "{van Leeuwen}, Wessel and Nguyen, {Dan T M} and Rianne Grond and Tineke Veenendaal and Catherine Rabouille and Far{\'i}as, {Ginny G}",

note = "{\textcopyright} 2022. Published by The Company of Biologists Ltd.",

year = "2022",

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doi = "10.1242/jcs.260294",

language = "English",

volume = "135",

journal = "Journal of Cell Science",

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T1 - Stress-induced phase separation of ERES components into Sec bodies precedes ER exit inhibition in mammalian cells

AU - van Leeuwen, Wessel

AU - Nguyen, Dan T M

AU - Grond, Rianne

AU - Veenendaal, Tineke

AU - Rabouille, Catherine

AU - Farías, Ginny G

PY - 2022/12/1

Y1 - 2022/12/1

N2 - Phase separation of components of ER exit sites (ERES) into membraneless compartments, the Sec bodies, occurs in Drosophila cells upon exposure to specific cellular stressors, namely, salt stress and amino acid starvation, and their formation is linked to the early secretory pathway inhibition. Here, we show Sec bodies also form in secretory mammalian cells upon the same stress. These reversible and membraneless structures are positive for ERES components, including both Sec16A and Sec16B isoforms and COPII subunits. We find that Sec16A, but not Sec16B, is a driver for Sec body formation, and that the coalescence of ERES components into Sec bodies occurs by fusion. Finally, we show that the stress-induced coalescence of ERES components into Sec bodies precedes ER exit inhibition, leading to their progressive depletion from ERES that become non-functional. Stress relief causes an immediate dissolution of Sec bodies and the concomitant restoration of ER exit. We propose that the 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.

AB - Phase separation of components of ER exit sites (ERES) into membraneless compartments, the Sec bodies, occurs in Drosophila cells upon exposure to specific cellular stressors, namely, salt stress and amino acid starvation, and their formation is linked to the early secretory pathway inhibition. Here, we show Sec bodies also form in secretory mammalian cells upon the same stress. These reversible and membraneless structures are positive for ERES components, including both Sec16A and Sec16B isoforms and COPII subunits. We find that Sec16A, but not Sec16B, is a driver for Sec body formation, and that the coalescence of ERES components into Sec bodies occurs by fusion. Finally, we show that the stress-induced coalescence of ERES components into Sec bodies precedes ER exit inhibition, leading to their progressive depletion from ERES that become non-functional. Stress relief causes an immediate dissolution of Sec bodies and the concomitant restoration of ER exit. We propose that the 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.

KW - Animals

KW - Endoplasmic Reticulum/metabolism

KW - COP-Coated Vesicles/metabolism

KW - Golgi Apparatus/metabolism

KW - Vesicular Transport Proteins/genetics

KW - Secretory Pathway

KW - Protein Transport

KW - Mammals/metabolism

U2 - 10.1242/jcs.260294

DO - 10.1242/jcs.260294

M3 - Article

C2 - 36325988

SN - 0021-9533

VL - 135

JO - Journal of Cell Science

JF - Journal of Cell Science

IS - 23

ER -

Stress-induced phase separation of ERES components into Sec bodies precedes ER exit inhibition in mammalian cells

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