The steroid hormone 20-hydroxyecdysone binds to dopamine receptor to repress lepidopteran insect feeding and promote pupation
Open accessAbstract
Holometabolous insects stop feeding at the final larval instar stage and then undergo metamorphosis; however, the mechanism is unclear. In the present study, using the serious lepidopteran agricultural pest Helicoverpa armigera as a model, we revealed that 20-hydroxyecdysone (20E) binds to the dopamine receptor (DopEcR), a G protein-coupled receptor, to stop larval feeding and promote pupation. DopEcR was expressed in various tissues and its level increased during metamorphic molting under 20E regulation. The 20E titer was low during larval feeding stages and high during wandering stages. By contrast, the dopamine (DA) titer was high during larval feeding stages and low during the wandering stages. Injection of 20E or blocking dopamine receptors using the inhibitor flupentixol decreased larval food consumption and body weight. Knockdown of DopEcR repressed larval feeding, growth, and pupation. 20E, via DopEcR, promoted apoptosis; and DA, via DopEcR, induced cell proliferation. 20E opposed DA function by repressing DA-induced cell proliferation and AKT phosphorylation. 20E, via DopEcR, induced gene expression and a rapid increase in intracellular calcium ions and cAMP. 20E induced the interaction of DopEcR with G proteins αs and αq. 20E, via DopEcR, induced protein phosphorylation and binding of the EcRB1-USP1 transcription complex to the ecdysone response element. DopEcR could bind 20E inside the cell membrane or after being isolated from the cell membrane. Mutation of DopEcR decreased 20E binding levels and related cellular responses. 20E competed with DA to bind to DopEcR. The results of the present study suggested that 20E, via binding to DopEcR, arrests larval feeding and promotes pupation.
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20E competes with dopamine to bind to DopEcR to block dopamine-mediated motor function and reward-motivated behavior, and initiates the 20E pathway.
“That study also demonstrates one of the mechanisms by which 20E represses larval feeding and promotes metamorphosis: 20E competes with dopamine to bind to DopEcR to block the dopamine-mediated motor function and reward-motivated behavior, and initiates the 20E pathway [49].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [49]
DopEcR in H. armigera can bind 20E in the cell membrane or as an isolated protein.
“DopEcR in H. armigera can bind 20E in the cell membrane or as an isolated protein [49].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [49]
20E-EIA detects the binding of GPCRs to 20E directly, presenting an alternative method to that using the isotope-labeled analog Pon A.
“20E-EIA detects the binding of GPCRs to 20E directly, presenting an alternative method to that using the isotope-labeled analog Pon A [49].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [49]
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Cites
Analyzing real-time PCR data by the comparative CT method
Schmittgen, T. D., & Livak, K. J. (2008) · Nature Protocols · doi:10.1038/nprot.2008.73 · Cited by 26,190 · see citing works
Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., & Mello, C. C. (1998) · Nature · doi:10.1038/35888 · Cited by 15,429 · see citing works
The physiology, signaling, and pharmacology of dopamine receptors
Beaulieu, J.-M., & Gainetdinov, R. R. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.002642 · Cited by 2,763 · see citing works
Zamore, P. D., Tuschl, T., Sharp, P. A., & Bartel, D. P. (2000) · Cell · doi:10.1016/s0092-8674(00)80620-0 · Cited by 2,667 · see citing works
Ligand docking and binding site analysis with PyMOL and Autodock/Vina
Seeliger, D., & de Groot, B. L. (2010) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-010-9352-6 · Cited by 2,648 · see citing works
A transmembrane intracellular estrogen receptor mediates rapid cell signaling
Revankar, C. M., Cimino, D. F., Sklar, L. A., Arterburn, J. B., & Prossnitz, E. R. (2005) · Science · doi:10.1126/science.1106943 · Cited by 2,302 · see citing works
G-protein-coupled receptors and signaling networks: emerging paradigms
Marinissen, M. J., & Gutkind, J. S. (2001) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01678-3 · Cited by 1,049 · see citing works
Multiple Actions of Steroid Hormones—A Focus on Rapid, Nongenomic Effects
Falkenstein, E., Tillmann, H.-C., Christ, M., Feuring, M., & Wehling, M. (2000) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01468-6 · Cited by 986 · see citing works
Functional ecdysone receptor is the product of EcR and Ultraspiracle genes
Yao, T., FORMAN, B. M., Jiang, Z., Cherbas, L., Chen, J.-D., McKeown, M., Cherbas, P. T., & Evans, R. M. (1993) · Nature · doi:10.1038/366476a0 · Cited by 947 · see citing works
Neve, K. A., Seamans, J. K., & Trantham‐Davidson, H. (2004) · Journal of Receptors and Signal Transduction · doi:10.1081/rrs-200029981 · Cited by 836 · see citing works
The Dynamic Process of β2-Adrenergic Receptor Activation
Nygaard, R., Zou, Y., Dror, R. O., Mildorf, T. J., Arlow, D. H., Manglik, A., Pan, A. C., Liu, C. W., Fung, J. J., Bokoch, M. P., et al. (2013) · Cell · doi:10.1016/j.cell.2013.01.008 · Cited by 797 · see citing works
Mechanism of dye response and interference in the Bradford protein assay
Compton, S. J., & Jones, C. G. (1985) · Analytical Biochemistry · doi:10.1016/0003-2697(85)90190-3 · Cited by 640 · see citing works
Estrogen Signaling Multiple Pathways to Impact Gene Transcription
Marino, M., Galluzzo, P., & Ascenzi, P. (2006) · Current Genomics · doi:10.2174/138920206779315737 · Cited by 618 · see citing works
Layered reward signalling through octopamine and dopamine in Drosophila
Burke, C. J., Huetteroth, W., Owald, D., Perisse, E., Krashes, M. J., Das, G., Gohl, D., Silies, M., Certel, S., & Waddell, S. (2012) · Nature · doi:10.1038/nature11614 · Cited by 614 · see citing works
Riddiford, L. M., Hiruma, K., Zhou, X., & Nelson, C. A. (2003) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2003.06.001 · Cited by 547 · see citing works
The Neurobiology of Dopamine Signaling
Girault, J., & Greengard, P. (2004) · Archives of Neurology · doi:10.1001/archneur.61.5.641 · Cited by 443 · see citing works
Selectivity determinants of GPCR–G-protein binding
Flock, T., Hauser, A. S., Lund, N., Gloriam, D. E., Balaji, S., & Babu, M. M. (2017) · Nature · doi:10.1038/nature22070 · Cited by 384 · see citing works
Hormonal cross talk in insect development
Dubrovsky, E. B. (2004) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2004.11.003 · Cited by 362 · see citing works
The unfolding stories of GPR30, a new membrane-bound estrogen receptor
Maggiolini, M., & Picard, D. (2010) · Journal of Endocrinology · doi:10.1677/joe-09-0242 · Cited by 360 · see citing works
Inagaki, H. K., Ben-Tabou de-Leon, S., Wong, A. M., Jagadish, S., Ishimoto, H., Barnea, G., Kitamoto, T., Axel, R., & Anderson, D. J. (2012) · Cell · doi:10.1016/j.cell.2011.12.022 · Cited by 325 · see citing works
“Is dopamine involved in Alzheimer's disease?”
Martorana, A., & Koch, G. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00252 · Cited by 276 · see citing works
Srivastava, D. P., Yu, E. J., Kennedy, K., Chatwin, H., Reale, V., Hamon, M., Smith, T., & Evans, P. D. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1005-05.2005 · Cited by 272 · see citing works
Distinct Dopamine Receptor Pathways Underlie the Temporal Sensitivity of Associative Learning
Handler, A., Graham, T. G. W., Cohn, R., Morantte, I. G., Siliciano, A. F., Zeng, J., Li, Y., & Ruta, V. (2019) · Cell · doi:10.1016/j.cell.2019.05.040 · Cited by 227 · see citing works
Dopamine D3 receptor as a therapeutic target for antipsychotic and antiparkinsonian drugs.
Joyce, J. N. (2001) · Pharmacology and Therapeutics · doi:10.1016/s0163-7258(01)00139-5 · Cited by 204 · see citing works
Ma, Z., Guo, W., Guo, X., Wang, X., & Kang, L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015098108 · Cited by 201 · see citing works
Renal Dopamine Receptors and Hypertension
Hussain, T., & Lokhandwala, M. F. (2003) · Experimental Biology and Medicine · doi:10.1177/153537020322800202 · Cited by 187 · see citing works
Kebabian, J. W. (1978) · Life Sciences · doi:10.1016/0024-3205(78)90157-1 · Cited by 154 · see citing works
Bombyx EcR (BmEcR) and Bombyx USP (BmCF1) combine to form a functional ecdysone receptor
Swevers, L., Cherbas, L., Cherbas, P. T., & Iatrou, K. (1996) · Insect Biochemistry and Molecular Biology · doi:10.1016/0965-1748(95)00097-6 · Cited by 139 · see citing works
Roles of the insulin signaling pathway in insect development and organ growth
Lin, X., & Smagghe, G. J. (2018) · Peptides · doi:10.1016/j.peptides.2018.02.001 · Cited by 133 · see citing works
Hedonic Eating and the “Delicious Circle”: From Lipid-Derived Mediators to Brain Dopamine and Back
Coccurello, R., & Maccarrone, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00271 · Cited by 133 · see citing works
Krolick, K. N., Zhu, Q., & Shi, H. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2018.07.008 · Cited by 121 · see citing works
Dopamine Receptor Signaling and Current and Future Antipsychotic Drugs
Boyd, K. N., & Mailman, R. B. (2012) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-25761-2_3 · Cited by 107 · see citing works
Lan, Q., Hiruma, K., Hu, X., Jindra, M., & Riddiford, L. M. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.7.4897 · Cited by 107 · see citing works
Reward-Induced Eating: Therapeutic Approaches to Addressing Food Cravings
Rebello, C. J., & Greenway, F. L. (2016) · Advances in Therapy · doi:10.1007/s12325-016-0414-6 · Cited by 105 · see citing works
Preininger, A. M., Meiler, J., & Hamm, H. E. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.04.011 · Cited by 104 · see citing works
Wang, S., Liu, S., Liu, H., Wang, J., Zhou, S., Jiang, R., Bendena, W. G., & Li, S. (2010) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjq006 · Cited by 94 · see citing works
Self-citationIshimoto, H., Wang, Z., Rao, Y., Wu, C., & Kitamoto, T. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003843 · Cited by 81 · see citing works
Establishment of a New Cell Line from Lepidopteran Epidermis and Hormonal Regulation on the Genes
Shao, H., Zheng, W., Liu, P., Wang, Q., Wang, J., & Zhao, X. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003127 · Cited by 79 · see citing works
Self-citationRNA Interference in Moths: Mechanisms, Applications, and Progress
Xu, J., Wang, X., Chen, P., Fang-tao, L., Zheng, S., Ye, H., & Mo, M. (2016) · Genes · doi:10.3390/genes7100088 · Cited by 72 · see citing works
Binding Kinetics and Pathways of Ligands to GPCRs
Straßer, A., Wittmann, H., & Seifert, R. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.05.005 · Cited by 67 · see citing works
Efficiency of Different Methods for dsRNA Delivery in Cotton Bollworm (Helicoverpa armigera)
Yang, J., & Han, Z. (2014) · Journal of Integrative Agriculture · doi:10.1016/s2095-3119(13)60511-0 · Cited by 66 · see citing works
Minakuchi, C., Nakagawa, Y., Kamimura, M., & Miyagawa, H. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03801.x · Cited by 64 · see citing works
Two dopamine receptors play different roles in phase change of the migratory locust
Guo, X., Ma, Z., & Kang, L. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00080 · Cited by 63 · see citing works
Liu, W., Cai, M.-J., Zheng, C.-C., Wang, J.-X., & Zhao, X.-F. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.547018 · Cited by 59 · see citing works
Self-citationPresence of membrane ecdysone receptor in the anterior silk gland of the silkworm <i>Bombyx mori</i>
Elmogy, M., Iwami, M., & Sakurai, S. (2004) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.2004.04249.x · Cited by 57 · see citing works
Vines, C. M. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-2888-2_10 · Cited by 52 · see citing works
Chapter 26 Agonist-specific coupling of G-protein-coupled receptors to second-messenger systems
Evans, P. D., Robb, S., Cheek, T. R., Reale, V., Hannan, F., Swales, L. S., Hall, L. M., & Midgley, J. M. (1995) · Progress in brain research · doi:10.1016/s0079-6123(08)61222-4 · Cited by 47 · see citing works
Abrieux, A., Duportets, L., Debernard, S., Gadenne, C., & Anton, S. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00312 · Cited by 45 · see citing works
G-protein-coupled receptor participates in 20-hydroxyecdysone signaling on the plasma membrane
Cai, M.-J., Dong, D.-J., Wang, Y., Liu, P.-C., Liu, W., Wang, J.-X., & Zhao, X.-F. (2014) · Cell Communication and Signaling · doi:10.1186/1478-811x-12-9 · Cited by 44 · see citing works
Self-citationLark, A. R. S., Kitamoto, T., & Martin, J. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2017.05.015 · Cited by 39 · see citing works
Liu, W., Cai, M.-J., Wang, J.-X., & Zhao, X.-F. (2014) · Endocrinology · doi:10.1210/en.2013-2020 · Cited by 38 · see citing works
Self-citationManaboon, M., Iga, M., Iwami, M., & Sakurai, S. (2009) · Journal of Insect Physiology · doi:10.1016/j.jinsphys.2008.10.013 · Cited by 37 · see citing works
Dopamine receptor subtypes in the native human heart
Cavallotti, C. A. P., Mancone, M., Bruzzone, P., et al. (2010) · Heart and Vessels · doi:10.1007/s00380-009-1224-4 · Cited by 37 · see citing works
G-protein-coupled receptor controls steroid hormone signaling in cell membrane
Wang, D., Zhao, W.-L., Cai, M.-J., Wang, J.-X., & Zhao, X.-F. (2015) · Scientific Reports · doi:10.1038/srep08675 · Cited by 35 · see citing works
Self-citationDominick, O. S., & Truman, J. W. (1986) · Journal of Experimental Biology · doi:10.1242/jeb.121.1.133 · Cited by 32 · see citing works
Jing, Y.-P., Liu, W., Wang, J.-X., & Zhao, X.-F. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.622696 · Cited by 30 · see citing works
Self-citationJing, Y.-P., Wang, D., Han, X.-L., Dong, D.-J., Wang, J.-X., & Zhao, X.-F. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.706028 · Cited by 30 · see citing works
Self-citationG-protein αq participates in the steroid hormone 20-hydroxyecdysone nongenomic signal transduction
Ren, J., Li, X.-R., Liu, P.-C., Cai, M.-J., Liu, W., Wang, J.-X., & Zhao, X.-F. (2014) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.08.006 · Cited by 15 · see citing works
Self-citationThe knockdown of Ha-GRIM-19 by RNA interference induced programmed cell death
Dong, D.-J., Liu, P., Wang, J., & Zhao, X. (2010) · Amino Acids · doi:10.1007/s00726-010-0824-8 · Cited by 11 · see citing works
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- Authors
- Kang, X.-L., Zhang, J.-Y., Wang, D., Zhao, Y.-M., Han, X.-L., Wang, J.-X., & Zhao, X.-F.
- Affiliations
- Shandong University (CN)
- Corresponding author
- Zhao, Xiao-Fan
- Venue
- PLOS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2019-08-14
- Volume
- 15
- Issue
- 8
- Pages
- e1008331
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC6693746
- OpenAlex
- W2968995517
- Cited by
- 96
- References
- 59
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 15 · 2023: 18 · 2022: 14 · 2021: 22 · 2020: 9
- FWCI
- 5.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Natural Science Foundation of China-Yunnan Joint Fund (31730083, 31572328)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Insect Resistance and Genetics
- Keywords
- 20-hydroxyecdysone, dopamine receptors, Helicoverpa armigera, pupation, metamorphosis, G protein-coupled receptors, ecdysone receptor, Akt phosphorylation, apoptosis, cell proliferation, intracellular calcium, cAMP signaling, G protein alpha subunit, ecdysone response element, insect molting
- MeSH terms
- Animals, Dopamine, Ecdysterone, Feeding Behavior, Flupenthixol, Larva, Moths, Receptors, Dopamine, Dopamine Antagonists, Molting, Insect Proteins, RNA Interference, Gene Knockdown Techniques, Sf9 Cells
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