4.6 Article

β-Arrestin1 interacts with G protein-coupled receptor to desensitize signaling of the steroid hormone 20-hydroxyecdysone in the lepidopteran insect Helicoverpa armigera

Journal

CELLULAR SIGNALLING
Volume 27, Issue 4, Pages 878-886

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2015.01.016

Keywords

Steroid hormone; 20-Hydroxyecdysone; beta-Arrestin1; G protein-coupled receptor; Signal desensitization

Categories

Funding

  1. National Natural Science Foundation of China [31230067]
  2. National Basic Research Program of China (973 Program) [2012CB114101]
  3. Ph.D. Programs Foundation of the Ministry of Education of China [20120131110025]

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The steroid hormone 20-hydroxyecdysone (20E) plays a critical role in insect development, particularly in larval molting and larval-pupal transition. Studies have indicated that 20E transmits its signal via a G protein-coupled receptor (GPCR)-mediated non-genomic pathway before a genomic pathway is initiated. However, the mechanism by which a 20E signal is desensitized remains unclear. We proposed that beta-arrestin1 interacts with ecdysone-responsible GPCR (ErGPCR1) to desensitize a 20E signal in the lepidopteran insect Helicoverpa armigera. Results showed that beta-arrestin1 was highly expressed in various tissues during metamorphosis. beta-Arrestin1 knockdown by RNA interference in larvae caused advanced pupation and a larval-pupal chimera. The mRNA levels of 20E-response genes were increased after beta-arrestin1 was knocked down but were decreased after beta-arrestin1 was overexpressed. 20E induced the migration of beta-arrestin1 from the cytosol to the cytoplasmic membrane to interact with ErGPCR1. The inhibitors suramin and chelerythrine chloride repressed 20E-induced beta-arrestin1 phosphotylation and membrane migration. With ErGPCR1, 20E regulated beta-arrestin1 phosphorylation on serines at positions 170 and 234. The double mutation of the amino acids Ser170 and Ser234 to asparagine inhibited phosphorylation and membrane migration of beta-arrestin1 in 20E induction. Therefore, 20E via ErGPCR1 and PKC signaling induces beta-arrestin1 phosphorylation; phosphorylated beta-arrestin1 migrates to the cytoplasmic membrane to interact with ErGPCR1 to block 20E signaling via a feedback mechanism. (c) 2015 Elsevier Inc All rights reserved.

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