Open AccessActivation of IRE1, PERK and salt-inducible kinases leads to Sec body formation in Drosophila S2 cells
Author(s) -
Chujun Zhang,
Wessel van Leeuwen,
Marloes Blotenburg,
Angelica Aguilera-Gomez,
Sem Brussee,
Rianne Grond,
Harm H. Kampinga,
Cathérine Rabouille
Publication year - 2021
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.258685
Subject(s) - endoplasmic reticulum , unfolded protein response , biology , microbiology and biotechnology , kinase , amino acid , eif 2 kinase , biochemistry , protein kinase a , cyclin dependent kinase 2
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.