The homotetramerization of a GPCR transmits the 20-hydroxyecdysone signal and increases its entry into cells for insect metamorphosis
The homotetramerization of a GPCR transmits the 20-hydroxyecdysone signal and increases its entry into cells for insect metamorphosis
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GPCR 的同四聚化可传递 20-羟基蜕皮激素信号并增加其进入昆虫变态细胞的机会
DOI：
10.1242/dev.196667
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发表时间：
2021-03-01
期刊：
影响因子：
4.6
通讯作者：
Zhao, Xiao-Fan
中科院分区：
文献类型：
--
作者：
Kang, Xin-Le;Li, Yan-Xue;Zhao, Xiao-Fan
ABSTRACT Animal steroid hormones initiate signaling by passive diffusion into cells and binding to their nuclear receptors to regulate gene expression. Animal steroid hormones can initiate signaling via G protein-coupled receptors (GPCRs); however, the underlying mechanisms are unclear. Here, we show that a newly discovered ecdysone-responsive GPCR, ErGPCR-3, transmits the steroid hormone 20-hydroxyecdysone (20E) signal by binding 20E and promoting its entry into cells in the lepidopteran insect Helicoverpa armigera. Knockdown of ErGPCR-3 in larvae caused delayed and abnormal pupation, inhibited remodeling of the larval midgut and fat body, and repressed 20E-induced gene expression. Also, 20E induced both the interaction of ErGPCR-3 with G proteins and rapid intracellular increase in calcium, cAMP and protein phosphorylation. ErGPCR-3 was endocytosed by GPCR kinase 2-mediated phosphorylation, and interacted with β-arrestin-1 and clathrin, to terminate 20E signaling under 20E induction. We found that 20E bound to ErGPCR-3 and induced the ErGPCR-3 homodimer to form a homotetramer, which increased 20E entry into cells. Our study revealed that homotetrameric ErGPCR-3 functions as a cell membrane receptor and increases 20E diffusion into cells to transmit the 20E signal and promote metamorphosis. Summary: Homotetramerization of ErGPCR-3 induced by 20E binding suggests a GPCR-mediated mechanism of 20E cell entry, which provides important implications for controlling wing disk and midgut development during metamorphosis.
