Cited by 16Ion Channels and ReceptorsCalcium signaling and nucleotide metabolismIon channel regulation and function

The steroid hormone 20-hydroxyecdysone induces phosphorylation and aggregation of stromal interacting molecule 1 for store-operated calcium entry

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Chen, Cai-Hua, Di, Yu-Qin, Shen, Qin-Yong, Wang, Jin-Xing, Zhao, Xiao-Fan·2019·Journal of Biological Chemistry

Abstract

Oligomerization of stromal interacting molecule 1 (STIM1) promotes store-operated calcium entry (SOCE); however, the mechanism of STIM1 aggregation is unclear. Here, using the lepidopteran insect and agricultural pest cotton bollworm ( Helicoverpa armigera ) as a model and immunoblotting, RT-qPCR, RNA interference (RNAi), and ChIP assays, we found that the steroid hormone 20-hydroxyecdysone (20E) up-regulates STIM1 expression via G protein–coupled receptors (GPCRs) and the 20E nuclear receptor (EcRB1). We also identified an ecdysone-response element (EcRE) in the 5′-upstream region of the STIM1 gene and also noted that STIM1 is located in the larval midgut during metamorphosis. STIM1 knockdown in larvae delayed pupation time, prevented midgut remodeling, and decreased 20E-induced gene transcription. STIM1 knockdown in a H. armigera epidermal cell line, HaEpi, repressed 20E-induced calcium ion influx and apoptosis. Moreover, 20E-induced STIM1 clustering to puncta and translocation toward the cell membrane. Inhibitors of GPCRs, phospholipase C (PLC), and inositol trisphosphate receptor (IP3R) repressed 20E-induced STIM1 phosphorylation, and we found that two GPCRs are involved in 20E-induced STIM1 phosphorylation. 20E-induced STIM1 phosphorylation on Ser-485 through protein kinase C (PKC), and we observed that Ser-485 phosphorylation is critical for STIM1 clustering, interaction with calcium release-activated calcium channel modulator 1 (Orai1), calcium ion influx, and 20E-induced apoptosis. These results suggest that 20E up-regulates STIM1 phosphorylation for aggregation via GPCRs, followed by interaction with Orai1 to induce SOCE, thereby promoting apoptosis in the midgut during insect metamorphosis.

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Authors
Chen, C.-H., Di, Y.-Q., Shen, Q.-Y., Wang, J.-X., & Zhao, X.-F.
Affiliations
Shandong University (CN)
Corresponding author
Zhao, Xiao-Fan
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2019-10
Volume
294
Issue
41
Pages
14922-14936
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2968469014
Cited by
16
References
67
Citations by year
2026: 3 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 3
FWCI
1.14
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (31730083, 31572328)
Topics
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
20-hydroxyecdysone, STIM1, store-operated calcium entry, ecdysone receptor, G protein-coupled receptors, Orai1, insect metamorphosis, apoptosis, ecdysone response element, Helicoverpa armigera, protein kinase C, phospholipase C, IP3 receptor
MeSH terms
Stromal Interaction Molecule 1, Animals, Biological Transport, Calcium, Ecdysterone, Larva, Lepidoptera, Metamorphosis, Biological, Phosphorylation, Signal Transduction, Up-Regulation, Apoptosis, Gene Expression Regulation, Developmental, Receptors, G-Protein-Coupled, Gene Knockdown Techniques, Protein Aggregates

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