Prediction of the post-translational modifications of adipokinetic hormone receptors from solitary to eusocial bees

Huipeng Yang, Jiaxing Huang, Yanjie Liu, Jilian Li, Shudong Luo, Jie Wu


Adipokinetic hormone receptor (AKHR) was regarded as the crucial regulator of lipid consuming, but now has been renewed as a pluripotent neuropeptide G protein-coupled receptor. It has been identified in all sequenced bee genomes from the solitary to the eusocial. In the current study, we try to clarify the transitions of AKHR on lipid utilization and other potential functions from solitary to eusocial bees. The results showed that the AKHRs were divided into different groups based on their social complexity approximately. Nevertheless, the critical motifs and tertiary structures were highly conserved. As to the post-translational modifications, the eusocial possessed more phosphorylation residues and modification patterns, which might be due to the necessity of more diverse functions. These results suggest that AKHRs are highly conserved on both primary motifs and tertiary structures, but more flexible on post-translational modifications so as to accommodate to more complicated eusocial life.


AKHR; Bee; GPCR; Homology modelling; Post-translational modifications; Eusocial evolution

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Ament, S. A., Q. W. Chan, M. M. Wheeler, S. E. Nixon, S. P. Johnson, S. L. Rodriguez-Zas, L. J. Foster & G. E. Robinson (2011). “Mechanisms of stable lipid loss in a social insect.” The Journal of Experimental Biology, 214: 3808-3821. doi: 10.1242/jeb.060244.

Bednarova, A., D. Kodrik & N. Krishnan (2013). “Adipokinetic hormone exerts its anti-oxidative effects using a conserved signal-transduction mechanism involving both PKC and cAMP by mobilizing extra- and intracellular Ca2+ stores.” Comparative Biochemistry and Physiology. Toxicology and Pharmacology, 158: 142-149. doi: 10.1016/j.cbpc.2013.07.002.

Bednarova, A., D. Kodrik & N. Krishnan (2015). “Knockdown of adipokinetic hormone synthesis increases susceptibility to oxidative stress in Drosophila-a role for dFoxO?” Comparative Biochemistry and Physiology. Toxicology and Pharmacology, 171: 8-14. doi: 10.1016/j.cbpc.2015.03.006.

Biasini, M., S. Bienert, A. Waterhouse, K. Arnold, G. Studer, T. Schmidt, F. Kiefer, T. Gallo Cassarino, M. Bertoni, L. Bordoli & T. Schwede (2014). “SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information.” Nucleic Acids Research, 42(W1): W252-W258.doi: 10.1093/nar/gku340.

Blom, N., S. Gammeltoft &S. Brunak (1999). “Sequence and structure-based prediction of eukaryotic protein phosphorylation sites.” Journal of Molecular Biology, 294: 1351-1362. doi: 10.1006/jmbi.1999.3310.

Blom, N., T. Sicheritz-Ponten, R. Gupta, S. Gammeltoft & S. Brunak (2004). “Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence.” Proteomics, 4: 1633-1649. doi: 10.1002/pmic.200300771.

Boerjan, B., D. Cardoen, A. Bogaerts, B. Landuyt, L. Schoofs & P. Verleyen (2010). “Mass spectrometric profiling of (neuro) - peptides in the worker honeybee, Apis mellifera.” Neuropharmacology, 58: 248-258. doi: 10.1016/j.neuropharm. 2009.06.026.

Caers, J., H. Verlinden, S. Zels, H. P. Vandersmissen, K. Vuerinckx &L. Schoofs (2012). “More than two decades of research on insect neuropeptide GPCRs: an overview.” Frontiers in Endocrinology, 3: 151. doi: 10.3389/fendo.2012.00151.

Collin, C., F. Hauser, P. Krogh-Meyer, K. K. Hansen, E. Gonzalez de Valdivia, M. Williamson & C. J. Grimmelikhuijzen (2011). “Identification of the Drosophila and Tribolium receptors for the recently discovered insect RYamide neuropeptides.” Biochemical and Biophysical Research Communications, 412: 578-583. doi: 10.1016/j.bbrc.2011.07.131.

Crailsheim, K. (1988). “Intestinal transport of sugars in the honeybee (Apis mellifera L.).” Journal of Insect Physiology, 34: 839-845.doi: 10.1016/0022-1910(88)90117-5.

Gade, G. & L. Auerswald (2003). “Mode of action of neuropeptides from the adipokinetic hormone family.” General and Comparative Endocrinology, 132: 10-20. doi: S00166 4800300159X [pii].

Galikova, M., M. Diesner, P. Klepsatel, P. Hehlert, Y. Xu, I. Bickmeyer, R. Predel & R. P. Kuhnlein (2015). “Energy homeostasis control in Drosophila adipokinetic hormone mutants.” Genetics, 201: 665-683. doi: 10.1534/genetics. 115.178897.

Gether, U. (2000). “Uncovering molecular mechanisms involved in activation of G protein-coupled receptors.” Endocrine Reviews, 21: 90-113. doi: 10.1210/edrv.21.1.0390.

Goddard, A. D. & A. Watts (2012). “Regulation of G protein-coupled receptors by palmitoylation and cholesterol.” BMC Biology, 10: 27. doi: 10.1186/1741-7007-10-27.

Hauser, F. & C. J. Grimmelikhuijzen (2014). “Evolution of the AKH/corazonin/ACP/GnRH receptor superfamily and their ligands in the Protostomia.” General and Comparative Endocrinology, 209: 35-49. doi: 10.1016/j.ygcen.2014.07.009.

Huang, H., X. Deng, X. He, W. Yang, G. Li, Y. Shi, L. Shi, L. Mei, J. Gao & N. Zhou (2011). “Identification of distinct c-terminal domains of the Bombyx adipokinetic hormone receptor that are essential for receptor export, phosphorylation and internalization.” Cellular Signalling, 23: 1455-1465. doi: 10.1016/j.cellsig.2011.04.006.

Isabel, G., J. R. Martin, S. Chidami, J. A. Veenstra & P. Rosay (2005). “AKH-producing neuroendocrine cell ablation decreases trehalose and induces behavioral changes in Drosophila.” American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 288: R531-R538. doi: 10.1152/ajpregu.00158.2004.

Kapheim, K.M., H. Pan, C. Li, S.L. Salzberg, D. Puiu, T. Magoc, H.M. Robertson, M.E. Hudson, A. Venkat, B.J. Fischman, A. Hernandez, M. Yandell, D. Ence, C. Holt, G.D. Yocum, W.P. Kemp, J. Bosch, R.M. Waterhouse, E.M. Zdobnov, E. Stolle, F.B. Kraus, S. Helbing, R.F.A. Moritz, K.M. Glastad, B.G. Hunt, M.A.D. Goodisman, F. Hauser, C.J.P. Grimmelikhuijzen, D.G. Pinheiro, F.M.F. Nunes, M. P.M. Soares, É.D. Tanaka, Z.L.P. Simões, K. Hartfelder, J.D. Evans, S.M. Barribeau, R.M. Johnson, J.H. Massey, B.R. Southey, M. Hasselmann, D. Hamacher, M. Biewer, C.F. Kent, A. Zayed, C. Blatti, S. Sinha, J.S. Johnston, S.J. Hanrahan, S.D. Kocher, J. Wang, G.E. Robinson & G. Zhang (2015). “Genomic signatures of evolutionary transitions from solitary to group living.” Science, 348(6239): 1139-1143. doi: 10.1126/science.aaa4788.

Kim, J. & T. P. Neufeld (2015). “Dietary sugar promotes systemic TOR activation in Drosophila through AKH-dependent selective secretion of Dilp3.” Nature Communications, 6: 6846. doi: 10.10 38/ncomms7846.

Lagerstrom, M.C. & H.B. Schioth (2008). “Structural diversity of G protein-coupled receptors and significance for drug discovery.” Nature Reviews Drug Discovery, 7: 339-357. doi: 10.1038/nrd2518.

Lorenz, M.W., R. Kellner, W. Völkl, K.H. Hoffmann & J. Woodring (2001). “A comparative study on hypertrehalosaemic hormones in the Hymenoptera: sequence determination, physiological actions and biological significance.” Journal of Insect Physiology, 47: 563-571. doi: 10.1016/S0022-1910(00)00133-5.

Malik, A., G. Gäde & A. B. Lange (2012). “Sequencing and biological effects of an adipokinetic/hypertrehalosemic peptide in the stick insect, Baculum extradentatum.” Peptides, 34: 51-56.doi: 10.1016/j.peptides.2011.08.005.

Mugumbate, G., G. E. Jackson & D. van der Spoel (2011). “Open conformation of adipokinetic hormone receptor from the malaria mosquito facilitates hormone binding.” Peptides, 32: 553-559.doi: 10.1016/j.peptides.2010.08.017.

Norskov-Lauritsen, L. & H. Brauner-Osborne (2015). “Role of post-translational modifications on structure, function and pharmacology of class C G protein-coupled receptors.” European Journal of Pharmacology, 763(Pt B): 233-240.doi: 10.1016/j.ejphar.2015.05.015.

Norskov-Lauritsen, L.,S. Jorgensen & H. Brauner-Osborne (2015). “N-glycosylation and disulfide bonding affects GPRC6A receptor expression, function, and dimerization.” FEBS Letters, 589(5): 588-597. doi: 10.1016/j.febslet.2015.01.019.

Nygaard, S., G. Zhang, M. Schiott, C. Li, Y. Wurm, H. Hu, J. Zhou, L. Ji, F. Qiu, M. Rasmussen, H. Pan, F. Hauser, A. Krogh, C. J. Grimmelikhuijzen, J. Wang & J. J. Boomsma (2011). “The genome of the leaf-cutting ant Acromyrmex echinatior suggests key adaptations to advanced social life and fungus farming.” Genome Research, 21: 1339-1348. doi: 10.1101/gr.121392.111.

Panzenböck, U. & K. Crailsheim (1997). “Glycogen in honeybee queens, workers and drones (Apis mellifera carnica Pollm.).” Journal of Insect Physiology, 43: 155-165. doi: 10.1016/S0022-1910(96)00079-0.

Staubli, F., T. J. Jorgensen, G. Cazzamali, M. Williamson, C. Lenz, L. Sondergaard, P. Roepstorff & C. J. Grimmelikhuijzen (2002). “Molecular identification of the insect adipokinetic hormone receptors.” Proceedings of the National Academy of Sciences of the United States of America, 99: 3446-3451. doi: 10.1073/pnas.052556499.

Sturm, S., D. Ramesh, A. Brockmann, S. Neupert & R. Predel (2016). “Agatoxin-like peptides in the neuroendocrine system of the honey bee and other insects.” Journal of Proteomics, 132: 77-84. doi: 10.1016/j.jprot.2015.11.021.

Tamura, K., G. Stecher, D. Peterson, A. Filipski & S. Kumar (2013). “MEGA6: molecular evolutionary genetics analysis version 6.0.” Molecular Biology and Evolution, 30: 2725-2729. doi: 10.1093/molbev/mst197.

Tobin, A.B. (2008). “G-protein-coupled receptor phosphorylation: where, when and by whom.” British Journal of Pharmacology, 153 (Suppl 1): S167-S176. doi: 10.1038/sj.bjp.0707662.

Van der Horst, D. J. (2003). “Insect adipokinetic hormones: release and integration of flight energy metabolism.” Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 136: 217-226. doi: 10.1016/S1096-4959(03)00151-9.

Veenstra, J.A. & H. Khammassi (2017). “Rudimentary expression of RYamide in Drosophila melanogaster relative to other Drosophila species points to a functional decline of this neuropeptide gene.” Insect Biochemistry and Molecular Biology, 83: 68-79. doi: 10.1016/j.ibmb.2017.03.001.

Veenstra, J.A., L. Rodriguez & R.J. Weaver (2012). “Allatotropin, leucokinin and AKH in honey bees and other Hymenoptera.” Peptides, 35: 122-130. doi: 10.1016/j.peptides.2012.02.019.

Votavova, A., A. Tomcala, E. Kofronova, M. Kudzejova, J. Sobotnik, P. Jiros, O. Komzakova &I. Valterova (2015). “Seasonal dynamics in the chemistry and structure of the fat bodies of bumblebee queens.” PLoS ONE, 10(11): e0142261. doi: 10.1371/journal.pone.0142261.

Wang, R., K. Natarajan &D. H. Margulies (2009). “Structural basis of the CD8 alpha beta/MHC class I interaction: focused recognition orients CD8 beta to a T cell proximal position.” Journal of Immunology, 183: 2554-2564. doi: 10.4049/jimmunol.0901276.

Wang, Y., C. S. Brent, E. Fennern &G. V. Amdam (2012). “Gustatory perception and fat body energy metabolism are jointly affected by vitellogenin and juvenile hormone in honey bees.” PLoS Genetics, 8: e1002779. doi: 10.1371/journal.pgen.1002779.

Woodard, S. H., B. J. Fischman, A. Venkat, M. E. Hudson, K. Varala, S. A. Cameron, A. G. Clark &G. E. Robinson (2011). “Genes involved in convergent evolution of eusociality in bees.” Proceedings of the National Academy of Sciences of the United States of America, 108: 7472-7477. doi: 10.1073/pnas.1103457108.

Yang, F., X. Yu, C. Liu, C.-X. Qu, Z. Gong, H.-D. Liu, F.-H. Li, H.-M. Wang, D.-F. He, F. Yi, C. Song, C.-L. Tian, K.-H. Xiao, J.-Y. Wang &J.-P. Sun (2015). “Phospho-selective mechanisms of arrestin conformations and functions revealed by unnatural amino acid incorporation and 19F-NMR.” Nature Communications, 6: 8202. doi: 10.1038/ncomms9202.

Zandawala, M., Z. Hamoudi, A.B. Lange & I. Orchard (2015). “Adipokinetic hormone signalling system in the Chagas disease vector, Rhodnius prolixus.” Insect Molecular Biology, 24: 264-276. doi: 10.1111/imb.12157.

Zheng, H., E.A. Pearsall, D.P. Hurst, Y. Zhang, J. Chu, Y. Zhou, P.H. Reggio, H.H. Loh & P.Y. Law (2012). “Palmitoylation and membrane cholesterol stabilize mu-opioid receptor homodimerization and G protein coupling.” BMC Cell Biology, 13: 6. doi: 10.1186/1471-2121-13-6.



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