G-protein-coupled receptor controls steroid hormone signaling in cell membrane.
G-protein-coupled receptors (GPCRs) are involved in animal steroid hormone signaling, but their mechanism is unclear. In this research, we report that a GPCR called ErGPCR-2 controls steroid hormone 20-hydroxyecdysone (20E) signaling in the cell membrane of the lepidopteran insect Helicoverpa armigera. ErGPCR-2 was highly expressed during molting and metamorphosis. 20E, via ErGPCR-2, regulated rapid intracellular calcium increase, protein phosphorylation, gene transcription, and insect metamorphosis. ErGPCR-2 was located in the cell surface and was internalized by 20E induction. GPCR kinase 2 participated in 20E-induced ErGPCR-2 phosphorylation and internalization. The internalized ErGPCR-2 was degraded by proteases to desensitize 20E signaling. ErGPCR-2 knockdown suppressed the entrance of 20E analog [(3)H] ponasterone A ([(3)H]Pon A) into the cells. ErGPCR-2 overexpression or blocking of ErGPCR-2 internalization increased the entrance of [(3)H]Pon A into the cells. However, ErGPCR-2 did not bind to [(3)H]Pon A. Results suggest that ErGPCR-2 transmits steroid hormone 20E signaling and controls 20E entrance into cells in the cell membrane.
Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
Di
D
Wang
Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
Wen-Li
WL
Zhao
Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
Mei-Juan
MJ
Cai
Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
Jin-Xing
JX
Wang
Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
Xiao-Fan
XF
Zhao
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D004440:Ecdysone / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D020868:Gene Silencing / Q000187:drug effects; D006728:Hormones / Q000378:metabolism*; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D007915:Lepidoptera / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008954:Models, Biological; D018978:Molting / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013256:Steroids / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014316:Tritium / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D006728:Hormones; D019476:Insect Proteins; D043562:Receptors, G-Protein-Coupled; D013256:Steroids; D014316:Tritium; D004440:Ecdysone