title: β-Arrestin1 interacts with G protein-coupled receptor to desensitize signaling of the steroid hormone 20-hydroxyecdysone in the lepidopteran insect Helicoverpa armigera.
abstract: 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 β-arrestin1 interacts with ecdysone-responsible GPCR (ErGPCR1) to desensitize a 20E signal in the lepidopteran insect Helicoverpa armigera. Results showed that β-arrestin1 was highly expressed in various tissues during metamorphosis. β-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 β-arrestin1 was knocked down but were decreased after β-arrestin1 was overexpressed. 20E induced the migration of β-arrestin1 from the cytosol to the cytoplasmic membrane to interact with ErGPCR1. The inhibitors suramin and chelerythrine chloride repressed 20E-induced β-arrestin1 phosphorylation and membrane migration. With ErGPCR1, 20E regulated β-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 β-arrestin1 in 20E induction. Therefore, 20E via ErGPCR1 and PKC signaling induces β-arrestin1 phosphorylation; phosphorylated β-arrestin1 migrates to the cytoplasmic membrane to interact with ErGPCR1 to block 20E signaling via a feedback mechanism.
authors: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China.
authors: Xiao-Qian
authors: XQ
authors: Zhang
authors: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China.
authors: Xiang-Ru
authors: XR
authors: Li
authors: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China.
authors: Jing
authors: J
authors: Ren
authors: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China.
authors: Yong-Bo
authors: YB
authors: Li
authors: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China.
authors: Mei-Juan
authors: MJ
authors: Cai
authors: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China.
authors: Jin-Xing
authors: JX
authors: Wang
authors: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China. Electronic address: xfzhao@sdu.edu.cn.
authors: Xiao-Fan
authors: XF
authors: Zhao
mesh_terms: D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004441:Ecdysterone / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007915:Lepidoptera / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D008675:Metamorphosis, Biological; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D019476:Insect Proteins; D043562:Receptors, G-Protein-Coupled; D000071557:beta-Arrestins; D004441:Ecdysterone; D011493:Protein Kinase C
keywords: 20-Hydroxyecdysone; G protein-coupled receptor; Signal desensitization; Steroid hormone; β-Arrestin1