Activation of IRE1, PERK and salt-inducible kinases leads to Sec body formation in Drosophila S2 cells

Chujun Zhang; Wessel van Leeuwen; Marloes Blotenburg; Angelica Aguilera-Gomez; Sem Brussee; Rianne Grond; Harm H Kampinga; Catherine Rabouille

doi:10.1242/jcs.258685

Activation of IRE1, PERK and salt-inducible kinases leads to Sec body formation in Drosophila S2 cells

Chujun Zhang, Wessel van Leeuwen, Marloes Blotenburg, Angelica Aguilera-Gomez, Sem Brussee, Rianne Grond, Harm H Kampinga, Catherine Rabouille

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

6 Citations (Scopus)

Abstract

The phase separation of the non-membrane bound Sec bodies occurs in Drosophila S2 cells by coalescence of components of the endoplasmic reticulum (ER) exit sites under the stress of amino acid starvation. Here, we address which signaling pathways cause Sec body formation and find that two pathways are critical. The first is the activation of the salt-inducible kinases (SIKs; SIK2 and SIK3) by Na+ stress, which, when it is strong, is sufficient. The second is activation of IRE1 and PERK (also known as PEK in flies) downstream of ER stress induced by the absence of amino acids, which needs to be combined with moderate salt stress to induce Sec body formation. SIK, and IRE1 and PERK activation appear to potentiate each other through the stimulation of the unfolded protein response, a key parameter in Sec body formation. This work shows the role of SIKs in phase transition and re-enforces the role of IRE1 and PERK as a metabolic sensor for the level of circulating amino acids and salt. This article has an associated First Person interview with the first author of the paper.

Original language	English
Journal	Journal of Cell Science
Volume	134
Issue number	17
DOIs	https://doi.org/10.1242/jcs.258685
Publication status	Published - 01 Sept 2021

Keywords

Animals
Drosophila/metabolism
Endoplasmic Reticulum Stress
Humans
Protein Serine-Threonine Kinases/genetics
Unfolded Protein Response
eIF-2 Kinase/genetics

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title = "Activation of IRE1, PERK and salt-inducible kinases leads to Sec body formation in Drosophila S2 cells",

abstract = "The phase separation of the non-membrane bound Sec bodies occurs in Drosophila S2 cells by coalescence of components of the endoplasmic reticulum (ER) exit sites under the stress of amino acid starvation. Here, we address which signaling pathways cause Sec body formation and find that two pathways are critical. The first is the activation of the salt-inducible kinases (SIKs; SIK2 and SIK3) by Na+ stress, which, when it is strong, is sufficient. The second is activation of IRE1 and PERK (also known as PEK in flies) downstream of ER stress induced by the absence of amino acids, which needs to be combined with moderate salt stress to induce Sec body formation. SIK, and IRE1 and PERK activation appear to potentiate each other through the stimulation of the unfolded protein response, a key parameter in Sec body formation. This work shows the role of SIKs in phase transition and re-enforces the role of IRE1 and PERK as a metabolic sensor for the level of circulating amino acids and salt. This article has an associated First Person interview with the first author of the paper.",

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author = "Chujun Zhang and {van Leeuwen}, Wessel and Marloes Blotenburg and Angelica Aguilera-Gomez and Sem Brussee and Rianne Grond and Kampinga, {Harm H} and Catherine Rabouille",

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T1 - Activation of IRE1, PERK and salt-inducible kinases leads to Sec body formation in Drosophila S2 cells

AU - Zhang, Chujun

AU - van Leeuwen, Wessel

AU - Blotenburg, Marloes

AU - Aguilera-Gomez, Angelica

AU - Brussee, Sem

AU - Grond, Rianne

AU - Kampinga, Harm H

AU - Rabouille, Catherine

PY - 2021/9/1

Y1 - 2021/9/1

N2 - The phase separation of the non-membrane bound Sec bodies occurs in Drosophila S2 cells by coalescence of components of the endoplasmic reticulum (ER) exit sites under the stress of amino acid starvation. Here, we address which signaling pathways cause Sec body formation and find that two pathways are critical. The first is the activation of the salt-inducible kinases (SIKs; SIK2 and SIK3) by Na+ stress, which, when it is strong, is sufficient. The second is activation of IRE1 and PERK (also known as PEK in flies) downstream of ER stress induced by the absence of amino acids, which needs to be combined with moderate salt stress to induce Sec body formation. SIK, and IRE1 and PERK activation appear to potentiate each other through the stimulation of the unfolded protein response, a key parameter in Sec body formation. This work shows the role of SIKs in phase transition and re-enforces the role of IRE1 and PERK as a metabolic sensor for the level of circulating amino acids and salt. This article has an associated First Person interview with the first author of the paper.

AB - The phase separation of the non-membrane bound Sec bodies occurs in Drosophila S2 cells by coalescence of components of the endoplasmic reticulum (ER) exit sites under the stress of amino acid starvation. Here, we address which signaling pathways cause Sec body formation and find that two pathways are critical. The first is the activation of the salt-inducible kinases (SIKs; SIK2 and SIK3) by Na+ stress, which, when it is strong, is sufficient. The second is activation of IRE1 and PERK (also known as PEK in flies) downstream of ER stress induced by the absence of amino acids, which needs to be combined with moderate salt stress to induce Sec body formation. SIK, and IRE1 and PERK activation appear to potentiate each other through the stimulation of the unfolded protein response, a key parameter in Sec body formation. This work shows the role of SIKs in phase transition and re-enforces the role of IRE1 and PERK as a metabolic sensor for the level of circulating amino acids and salt. This article has an associated First Person interview with the first author of the paper.

KW - Animals

KW - Drosophila/metabolism

KW - Endoplasmic Reticulum Stress

KW - Humans

KW - Protein Serine-Threonine Kinases/genetics

KW - Unfolded Protein Response

KW - eIF-2 Kinase/genetics

U2 - 10.1242/jcs.258685

DO - 10.1242/jcs.258685

M3 - Article

C2 - 34350957

SN - 0021-9533

VL - 134

JO - Journal of Cell Science

JF - Journal of Cell Science

IS - 17

ER -

Activation of IRE1, PERK and salt-inducible kinases leads to Sec body formation in Drosophila S2 cells

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Keywords

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