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Latrophilin mediates insecticides susceptibility and fecundity through two carboxylesterases, esterase4 and esterase6, in Tribolium castaneum

  • L. Wei (a1), S. Gao (a1), W. Xiong (a1), J. Liu (a1), J. Mao (a1), Y. Lu (a1), X. Song (a1) and B. Li (a1)...


Latrophilin (LPH) is known as an adhesion G-protein-coupled receptor which involved in multiple physiological processes in organisms. Previous studies showed that lph not only involved the susceptibility to anticholinesterase insecticides but also affected fecundity in Tribolium castaneum. However, its regulatory mechanisms in these biological processes are still not clear. Here, we identified two potential downstream carboxylesterase (cce) genes of Tclph, esterase4 and esterase6, and further characterized their interactions with Tclph. After treatment of T. castaneum larvae with carbofuran or dichlorvos insecticides, the transcript levels of Tcest4 and Tcest6 were significantly induced from 12 to 72 h. RNAi against Tcest4 or Tcest6 led to the higher mortality compared with the controls after the insecticides treatment, suggesting that these two genes play a vital role in detoxification of insecticides in T. castaneum. Furthermore, with insecticides exposure to Tclph knockdown beetles, the expression of Tcest4 was upregulated but Tcest6 was downregulated, indicating that beetles existed a compensatory response against the insecticides. Additionally, RNAi of Tcest6 resulted in 43% reductions in female egg laying and completely inhibited egg hatching, which showed the similar phenotype as that of Tclph knockdown. These results indicated that Tclph affected fecundity by positively regulating Tcest6 expression. Our findings will provide a new insight into the molecular mechanisms of Tclph involved in physiological functions in T. castaneum.


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These authors contributed equally to this work

Postal address: Nanjing Normal University, #1 Wenyuan Road, Nanjing, China.



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Begum, K., Li, B., Beeman, R.W. & Park, Y. (2009) Functions of ion transport peptide and ion transport peptide-like in the red flour beetle Tribolium castaneum. Insect Biochemistry and Molecular Biology 39, 717725.10.1016/j.ibmb.2009.08.005
Bonaglia, M.C., Marelli, S., Novara, F., Commodaro, S., Borgatti, R., Minardo, G., Memo, L., Mangold, E., Beri, S. & Zucca, C. (2010) Genotype–phenotype relationship in three cases with overlapping 19p13. 12 microdeletions. European Journal of Human Genetics 18, 13021309.10.1038/ejhg.2010.115
Boucard, A.A., Maxeiner, S. & Südhof, T.C. (2014) Latrophilins function as heterophilic cell-adhesion molecules by binding to teneurins: regulation by alternative splicing. Journal of Biological Chemistry 289, 387402.10.1074/jbc.M113.504779
Chen, M.-L. & Chen, C.-H. (2005) Microarray analysis of differentially expressed genes in rat frontal cortex under chronic risperidone treatment. Neuropsychopharmacology 30, 268277.10.1038/sj.npp.1300612
Claudianos, C., Russell, R.J. & Oakeshott, J.G. (1999) The same amino acid substitution in orthologous esterases confers organophosphate resistance on the house fly and a blowfly. Insect Biochem Mol Biol 29, 675686.
De Silva, D. & Hemingway, J. (2002) Structural organization of the estalpha3(1) gene in a Colombian strain of Culex quinquefasciatus differs from that in Cuba. Medical and Veterinary Entomology 16, 99105.
Doyle, S.E., Scholz, M.J., Greer, K.A., Hubbard, A.D., Darnell, D.K., Antin, P.B., Klewer, S.E. & Runyan, R.B. (2006) Latrophilin-2 is a novel component of the epithelial-mesenchymal transition within the atrioventricular canal of the embryonic chicken heart. Dev Dyn 235, 32133221.10.1002/dvdy.20973
Durand, N., Chertemps, T., Francois, A., Rosell, G., Dekker, T., Lucas, P. & Maibeche-Coisne, M. (2014) In vivo characterization of an antennal carboxylesterase involved in pheromone response in Drosophila. In Proceedings of the Congress of the European-Chemoreception-Research-Organization, pp. 95.
Feng, Q.L., Ladd, T.R., Tomkins, B.L., Sundaram, M., Sohi, S.S., Retnakaran, A., Davey, K.G. & Palli, S.R. (1999) Spruce budworm (Choristoneura fumiferana) juvenile hormone esterase: hormonal regulation, developmental expression and cDNA cloning. Molecular and Cellular Endocrinology 148, 95108.
Gao, S., Liu, X., Liu, J., Xiong, W., Song, X., Wei, W., Wei, L. & Li, B. (2017) Identification and evolution of latrophilin receptor gene involved in Tribolium castaneum development and female fecundity. Genesis 55(12).
Gao, S., Xiong, W., Wei, L., Liu, J., Liu, X., Xie, J., Song, X., Bi, J. & Li, B. (2018) Transcriptome profiling analysis reveals the role of latrophilin in controlling development, reproduction and insecticide susceptibility in Tribolium castaneum. Genetica 146, 287302.10.1007/s10709-018-0020-4
Ge, L.Q., Huang, B., Jiang, Y.P., Gu, H.T., Xia, T., Yang, G.Q., Liu, F. & Wu, J.C. (2017) Carboxylesterase precursor (EST-1) mediated the fungicide jinggangmycin-suppressed reproduction of Sogatella furcifera (Hemiptera: Delphacidae). Journal of Economic Entomology 110, 21992206.10.1093/jee/tox201
Gilbert, D.G. & Richmond, R.C. (1982) Esterase 6 in Drosophila melanogaster: reproductive function of active and null males at low temperature. Proc Natl Acad Sci U S A 79, 29622966.
Hawkes, N.J. & Hemingway, J. (2002) Analysis of the promoters for the beta-esterase genes associated with insecticide resistance in the mosquito Culex quinquefasciatus. Biochimica et Biophysica Acta 1574, 5162.
Hirai, M., Kamimura, M., Kikuchi, K., Yasukochi, Y., Kiuchi, M., Shinoda, T. & Shiotsuki, T. (2002) cDNA cloning and characterization of Bombyx mori juvenile hormone esterase: an inducible gene by the imidazole insect growth regulator KK-42. Insect Biochemistry and Molecular Biology 32, 627635.
Ishida, Y. & Leal, W.S. (2005) Rapid inactivation of a moth pheromone. Proc Natl Acad Sci U S A 102, 1407514079.10.1073/pnas.0505340102
Kellendonk, C., Simpson, E.H. & Kandel, E.R. (2009) Modeling cognitive endophenotypes of schizophrenia in mice. Trends in Neurosciences 32, 347358.
Kim, Y.H., Issa, M.S., Cooper, A.M.W. & Zhu, K.Y. (2015) RNA interference: Applications and advances in insect toxicology and insect pest management. Pesticide Biochemistry & Physiology 120, 109117.10.1016/j.pestbp.2015.01.002
Krasnoperov, V.G., Bittner, M.A., Beavis, R., Kuang, Y., Salnikow, K.V., Chepurny, O.G., Little, A.R., Plotnikov, A.N., Wu, D. & Holz, R.W. (1997) α-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor. Neuron 18, 925.10.1016/S0896-6273(00)80332-3
Krishnamoorti, K. & Singh, A.K. (2017) Fitness differences due to allelic variation at Esterase-4 locus in Drosophila ananassae. Journal of Genetics 96, 625631.10.1007/s12041-017-0814-7
Lange, M., Norton, W., Coolen, M., Chaminade, M., Merker, S., Proft, F., Schmitt, A., Vernier, P., Lesch, K. & Bally-Cuif, L. (2012) The ADHD-susceptibility gene lphn3. 1 modulates dopaminergic neuron formation and locomotor activity during zebrafish development. Molecular psychiatry 17, 946954.
Langenhan, T. & Russ, A.P. (2010) Latrophilin signalling in tissue polarity and morphogenesis. Advances in Experimental Medicine and Biology 706, 3748.10.1007/978-1-4419-7913-1_3
Lelianova, V.G., Davletov, B.A., Sterling, A., Rahman, M.A., Grishin, E.V., Totty, N.F. & Ushkaryov, Y.A. (1997) Alpha-latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors. Journal of Biological Chemistry 272, 2150421508.10.1074/jbc.272.34.21504
Livak, K.J. & Schmittgen, T.D. (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25, 402408.
Lu, Y., Park, Y., Gao, X., Zhang, X., Yao, J., Pang, Y.P., Jiang, H. & Zhu, K.Y. (2012) Cholinergic and non-cholinergic functions of two acetylcholinesterase genes revealed by gene-silencing in Tribolium castaneum. Scientific Reports 2, 288.
Mee, C.J., Tomlinson, S.R., Perestenko, P.V., De, P.D., Duce, I.R., Usherwood, P.N. & Bell, D.R. (2004) Latrophilin is required for toxicity of black widow spider venom in Caenorhabditis elegans. Biochemical Journal 378, 185191.10.1042/bj20031213
Meza-Aguilar, D.G. & Boucard, A.A. (2014) Latrophilins updated. Biomolecular Concepts 5, 457478.10.1515/bmc-2014-0032
Muller, A., Winkler, J., Fiedler, F., Sastradihardja, T., Binder, C., Schnabel, R., Kungel, J., Rothemund, S., Hennig, C., Schoneberg, T. & Promel, S. (2015) Oriented cell division in the C. elegans embryo is coordinated by G-protein signaling dependent on the adhesion GPCR LAT-1. PLoS Genetics 11, e1005624.10.1371/journal.pgen.1005624
Newcomb, R.D., Campbell, P.M., Ollis, D.L., Cheah, E., Russell, R.J. & Oakeshott, J.G. (1997) A single amino acid substitution converts a carboxylesterase to an organophosphorus hydrolase and confers insecticide resistance on a blowfly. Proc Natl Acad Sci U S A 94, 74647468.
Oakeshott, J.G., Claudianos, C., Campbell, P.M., Newcomb, R.D. & Russell, R.J. (2005) 5.10 – biochemical genetics and genomics of insect esterases. Comprehensive Molecular Insect Science 5, 309381.
Oh, K.H. & Kim, H. (2017) Aldicarb-induced paralysis assay to determine defects in synaptic transmission in Caenorhabditis elegans. Bio-protocol 7(14).10.21769/BioProtoc.2400
Posbergh, C.J. (2015) A non-synonymous change in latrophilin-3 associated with equine degenerative myeloencephalopathy. In Proceedings of Plant and Animal Genome Conference (PAG XXIV), San Diego, CA, 10 - 14 January., p. 0338
Poupardin, R., Srisukontarat, W., Yunta, C. & Ranson, H. (2014) Identification of carboxylesterase genes implicated in temephos resistance in the dengue vector Aedes aegypti. PLoS Neglected Tropical Diseases 8, e2743.
Robin, C., Bardsley, L.M.J., Coppin, C. & Oakeshott, J.G. (2009) Birth and Death of Genes and Functions in the β-Esterase Cluster of Drosophila. Journal of Molecular Evolution 69, 1021.
Sabourault, C., Guzov, V.M., Koener, J.F., Claudianos, C., Plapp, F.W. Jr. & Feyereisen, R. (2001) Overproduction of a P450 that metabolizes diazinon is linked to a loss-of-function in the chromosome 2 ali-esterase (MdalphaE7) gene in resistant house flies. Insect Molecular Biology 10, 609618.
Schneider, C.A., Rasband, W.S. & Eliceiri, K.W. (2012) NIH image to ImageJ: 25 years of Image Analysis. Nature Methods 9, 671675.10.1038/nmeth.2089
Silva, J.P. & Ushkaryov, Y.A. (2010) The latrophilins, “split-personality” receptors. Adv Exp Med Biol 706, 5975.10.1007/978-1-4419-7913-1_5
Song, X., Huang, F., Liu, J., Li, C., Gao, S., Wu, W., Zhai, M., Yu, X., Xiong, W., Xie, J. & Li, B. (2017) Genome-wide DNA methylomes from discrete developmental stages reveal the predominance of non-CpG methylation in Tribolium castaneum. DNA Research 24, 445457.
Strode, C., Steen, K., Ortelli, F. & Ranson, H. (2006) Differential expression of the detoxification genes in the different life stages of the malaria vector Anopheles gambiae. Insect Mol Biol 15, 523530.
Sugita, S., Ichtchenko, K., Khvotchev, M. & Südhof, T.C. (1998) alpha-Latrotoxin receptor CIRL/latrophilin 1 (CL1) defines an unusual family of ubiquitous G-protein-linked receptors. G-protein coupling not required for triggering exocytosis. Journal of Biological Chemistry 273, 32715.10.1074/jbc.273.49.32715
Van Der Voet, M., Harich, B., Franke, B. & Schenck, A. (2016) ADHD-associated dopamine transporter, latrophilin and neurofibromin share a dopamine-related locomotor signature in Drosophila. Molecular Psychiatry 21, 565573.
Wallis, D., Hill, D.S., Mendez, I.A., Abbott, L.C., Finnell, R.H., Wellman, P.J. & Setlow, B. (2012) Initial characterization of mice null for Lphn3, a gene implicated in ADHD and addiction. Brain Research 1463, 8592.
Wang, L.L., Huang, Y., Lu, X.P., Jiang, X.Z., Smagghe, G., Feng, Z.J., Yuan, G.R., Wei, D. & Wang, J.J. (2015) Overexpression of two alpha-esterase genes mediates metabolic resistance to malathion in the oriental fruit fly, Bactrocera dorsalis (Hendel). Insect Molecular Biology 24, 467479.
Wang, S., Liu, Y., Zhou, J.J., Yi, J.K., Pan, Y., Wang, J., Zhang, X.X., Wang, J.X., Yang, S. & Xi, J.H. (2018) Identification and tissue expression profiling of candidate UDP-glycosyltransferase genes expressed in Holotrichia parallela motschulsky antennae. Bulletin of Entomological Research 108, 807816.
Xiong, W., Zhai, M., Yu, X., Wei, L., Mao, J., Liu, J., Xie, J. & Li, B. (2018) Comparative RNA-sequencing analysis of ER-based HSP90 functions and signal pathways in Tribolium castaneum. Cell Stress & Chaperones 23, 2943.
Yang, X.Q. (2016) Gene expression analysis and enzyme assay reveal a potential role of the carboxylesterase gene CpCE-1 from Cydia pomonella in detoxification of insecticides. Pesticide Biochemistry & Physiology 129, 5662.
Yu, Q.Y., Lu, C., Li, W.L., Xiang, Z.H. & Zhang, Z. (2009) Annotation and expression of carboxylesterases in the silkworm, Bombyx mori. BMC Genomics 10, 553.10.1186/1471-2164-10-553
Zhang, J., Li, D., Ge, P., Guo, Y., Zhu, K.Y., Ma, E. & Zhang, J. (2014a) Molecular and functional characterization of cDNAs putatively encoding carboxylesterases from the migratory locust, Locusta migratoria. PLoS One 9, e94809.
Zhang, J., Ge, P., Li, D., Guo, Y., Zhu, K.Y., Ma, E. & Zhang, J. (2015) Two homologous carboxylesterase genes from Locusta migratoria with different tissue expression patterns and roles in insecticide detoxification. Journal of Insect Physiology 77, 18.
Zhang, J., Li, D., Ge, P., Yang, M., Guo, Y., Zhu, K.Y., Ma, E. & Zhang, J. (2013) RNA interference revealed the roles of two carboxylesterase genes in insecticide detoxification in Locusta migratoria. Chemosphere 93, 12071215.
Zhang, Y.P., Song, D.N., Wu, H.H., Yang, H.M., Zhang, J.Z., Li, L.J., Ma, E.B. & Guo, Y.P. (2014b) Effect of dietary cadmium on the activity of glutathione S-transferase and carboxylesterase in different developmental stages of the Oxya chinensis (Orthoptera: Acridoidea). Environ Entomol 43, 171177.
Zhao, B., Bie, J., Wang, J., Marqueen, S.A. & Ghosh, S. (2012) Identification of a novel intracellular cholesteryl ester hydrolase (carboxylesterase 3) in human macrophages: compensatory increase in its expression after carboxylesterase 1 silencing. Am J Physiol Cell Physiol 303, C427435.


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Latrophilin mediates insecticides susceptibility and fecundity through two carboxylesterases, esterase4 and esterase6, in Tribolium castaneum

  • L. Wei (a1), S. Gao (a1), W. Xiong (a1), J. Liu (a1), J. Mao (a1), Y. Lu (a1), X. Song (a1) and B. Li (a1)...


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