Vitellogenin in Honey Bee Behavior and Lifespan

  • Gro V. AmdamEmail author
  • Erin Fennern
  • Heli Havukainen


Vitellogenin is a phospholipoglycoprotein that affects multiple aspects of honey bee life-history. Across the vast majority of oviparous taxa, vitellogenins are female-specific egg yolk proteins, with their essential function tied to oogenesis. In honey bees, however, vitellogenin is also expressed by female helpers, called workers, which are largely sterile. Here, vitellogenin influences behavior and stress resilience, and is believed to be important to honey bee social organization. Together with longtime collaborators, we have discovered roles of vitellogenin in worker behavioral traits such as nursing, foraging onset and foraging bias, and in survival traits such as oxidative stress resilience, cell-based immunity, and longevity. We have also identified a mutually inhibitory interaction between vitellogenin and the systemic endocrine factor juvenile hormone (JH), which is central to insect reproduction and stress response. This regulatory feedback loop has spurred hypotheses on how vitellogenin and JH together have become key life-history regulators in honey bees. A current research focus is on how this feedback loop is tied to nutrient-sensing insulin/insulin-like signaling that can govern expression of phenotypic plasticity. Here, we summarize this body of work in the context of new structural speculations that can lead to a modern understanding of vitellogenin function.


Juvenile Hormone Ethyl Oleate Stress Resilience Vitellogenin Gene Vitellogenin Synthesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Double repressor hypothesis


Juvenile hormone


Reproductive ground plan hypothesis




von Willebrand factor D-type


  1. 1.
    Alexandru G, Uhlmann F, Mechtler K, Poupart MA, Nasmyth K (2001) Phosphorylation of the cohesin subunit Scc1 by Polo/Cdc5 kinase regulates sister chromatid separation in yeast. Cell 105(4):459–472PubMedCrossRefGoogle Scholar
  2. 2.
    Amdam GV (2011) Social context, stress, and plasticity of aging. Aging Cell 10(1):18–27PubMedCrossRefGoogle Scholar
  3. 3.
    Amdam GV, Ihle KE, Page RE (2009) Regulation of honey bee (Apis mellifera) life histories by vitellogenin. In: Pfaff D, Arnold A, Etgen A, Fahrbach S, Rubin R (eds) Hormones, brain and behavior, 2nd edn. Elsevier Academic Press, San DiegoGoogle Scholar
  4. 4.
    Amdam GV, Norberg K, Fondrk MK, Page RE (2004) Reproductive ground plan may mediate colony-level selection effects on individual foraging behavior in honey bees. Proc Natl Acad Sci USA 101:11350–11355PubMedCrossRefGoogle Scholar
  5. 5.
    Amdam GV, Norberg K, Hagen A, Omholt SW (2003) Social exploitation of vitellogenin. Proc Natl Acad Sci USA 100:1799–1802PubMedCrossRefGoogle Scholar
  6. 6.
    Amdam GV, Omholt SW (2003) The hive bee to forager transition in honeybee colonies: the double repressor hypothesis. J Theor Biol 223:451–464PubMedCrossRefGoogle Scholar
  7. 7.
    Amdam GV, Seehuus SC (2006) Order, disorder, death: lessons from a superorganism. Adv Cancer Res 95:31–60PubMedCrossRefGoogle Scholar
  8. 8.
    Amdam GV, Simões ZLP, Guidugli KR, Norberg K, Omholt SW (2003) Disruption of vitellogenin gene function in adult honeybees by intra-abdominal injection of double-stranded RNA. BMC Biotechnol 3:1–8PubMedCrossRefGoogle Scholar
  9. 9.
    Amdam GV, Simões ZLP, Hagen A, Norberg K, Schrøder K et al (2004) Hormonal control of the yolk precursor vitellogenin regulates immune function and longevity in honeybees. Exp Gerontol 39:767–773PubMedCrossRefGoogle Scholar
  10. 10.
    Anderson TA, Levitt DG, Banaszak LJ (1998) The structural basis of lipid interactions in lipovitellin, a soluble lipoprotein. Struct Fold Des 6(7):895–909CrossRefGoogle Scholar
  11. 11.
    Bartke A (2005) Minireview: role of the growth hormone/insulin-like growth factor system in mammalian aging. Endocrinology 146(9):3718–3723PubMedCrossRefGoogle Scholar
  12. 12.
    Ben-Shahar Y, Dudek NL, Robinson GE (2004) Phenotypic deconstruction reveals involvement of manganese transporter malvolio in honey bee division of labor. J Exp Biol 207:3281–3288PubMedCrossRefGoogle Scholar
  13. 13.
    Ben-Shahar Y, Robichon A, Sokolowski MB, Robinson GE (2002) Influence of gene action across different time scales on behavior. Science 296:741–744PubMedCrossRefGoogle Scholar
  14. 14.
    Chen JS, Sappington TW, Raikhel AS (1997) Extensive sequence conservation among insect, nematode, and vertebrate vitellogenins reveals ancient common ancestry. J Mol Evol 44(4):440–451PubMedCrossRefGoogle Scholar
  15. 15.
    Cohen P (2000) The regulation of protein function by multisite phosphorylation – a 25 year update. Trends Biochem Sci 25(12):596–601PubMedCrossRefGoogle Scholar
  16. 16.
    Corona M, Velarde RA, Remolina S, Moran-Lauter A, Wang Y et al (2007) Vitellogenin, juvenile hormone, insulin signaling, and queen honey bee longevity. Proc Natl Acad Sci USA 104:7128–7133PubMedCrossRefGoogle Scholar
  17. 17.
    Crailsheim K (1990) The protein balance of the honey bee worker. Apidologie 21:417–429CrossRefGoogle Scholar
  18. 18.
    Dallman MF, Warne JP, Foster MT, Pecoraro NC (2007) Glucocorticoids and insulin both modulate caloric intake through actions on the brain. J Physiol 583:431–436PubMedCrossRefGoogle Scholar
  19. 19.
    DeLano WL (2002) The PyMOL molecular graphics system. De Lano Scientific, Palo AltoGoogle Scholar
  20. 20.
    Doucet N, Watt ED, Loria JP (2009) The flexibility of a distant loop modulates active site motion and product release in ribonuclease A. Biochemistry 48(30):7160–7168PubMedCrossRefGoogle Scholar
  21. 21.
    Engels W, Kaatz H, Zillikens A, Simões ZLP, Truve A et al (1990) Honey bee reproduction: vitellogenin and caste-specific regulation of fertility. In: Hoshi M, Yamashita O (eds) Advances in invertebrate reproduction, vol 5. Elsevier Science Publishers B.V., Amsterdam, pp 495–502Google Scholar
  22. 22.
    Flatt T, Min KJ, D’Alterio C, Villa-Cuesta E, Cumbers J et al (2008) Drosophila germ-line modulation of insulin signaling and lifespan. Proc Natl Acad Sci USA 105(17):6368–6373PubMedCrossRefGoogle Scholar
  23. 23.
    Grigg JC, Cooper JD, Cheung J, Heinrichs DE, Murphy ME (2010) The Staphylococcus aureus siderophore receptor HtsA undergoes localized conformational changes to enclose staphyloferrin A in an arginine-rich binding pocket. J Biol Chem 285(15):11162–11171PubMedCrossRefGoogle Scholar
  24. 24.
    Guidugli KR, Piulachs MD, Belles X, Lourenco AP, Simões ZLP (2005) Vitellogenin expression in queen ovaries and in larvae of both sexes of Apis mellifera. Arch Insect Biochem Physiol 59:211–218PubMedCrossRefGoogle Scholar
  25. 25.
    Havukainen H, Halskau Ø, Sjærven L, Amdam GV (2011) Deconstructing honeybee vitellogenin: novel 40 kDa fragment assigned to its N-terminus. J Exp Biol 214:582–592PubMedCrossRefGoogle Scholar
  26. 26.
    Huang Z-Y, Robinson GE (1996) Regulation of honey bee division of labor by colony age demography. Behav Ecol Sociobiol 39:147–158CrossRefGoogle Scholar
  27. 27.
    Jones DT (1999) Protein secondary structure prediction based on position-specific scoring matrices. J Mol Biol 292(2):195–202PubMedCrossRefGoogle Scholar
  28. 28.
    Leoncini I, Le Conte Y, Costagliola G, Plettner E, Toth AL et al (2004) Regulation of behavioral maturation by a primer pheromone produced by adult worker honey bees. Proc Natl Acad Sci USA 101(50):17559–17564PubMedCrossRefGoogle Scholar
  29. 29.
    Li A, Sadasivam M, Ding JL (2003) Receptor-ligand interaction between vitellogenin receptor (VtgR) and vitellogenin (Vtg), implications on low density lipoprotein receptor and apolipoprotein B/E. The first three ligand-binding repeats of VtgR interact with the amino-terminal region of Vtg. J Biol Chem 278(5):2799–2806PubMedCrossRefGoogle Scholar
  30. 30.
    Marco Antonio DS, Guidugli-Lazzarini KR, Nascimento AM, Simões ZLP, Hartfelder K (2008) RNAi-mediated silencing of vitellogenin gene function turns honeybee (Apis mellifera) workers into extremely precocious foragers. Naturwissenschaften 95:953–961PubMedCrossRefGoogle Scholar
  31. 31.
    Menzel R, Leboulle G, Eisenhardt D (2006) Small brains, bright minds. Cell 124:237–239PubMedCrossRefGoogle Scholar
  32. 32.
    Nelson CM, Ihle K, Amdam GV, Fondrk MK, Page RE (2007) The gene vitellogenin has multiple coordinating effects on social organization. PLoS Biol 5:673–677CrossRefGoogle Scholar
  33. 33.
    Piulachs MD, Guidugli KR, Barchuk AR, Cruz J, Simões ZLP et al (2003) The vitellogenin of the honey bee, Apis mellifera: structural analysis of the cDNA and expression studies. Insect Biochem Mol Biol 33:459–465PubMedCrossRefGoogle Scholar
  34. 34.
    Raag R, Appelt K, Xuong NH, Banaszak L (1988) Structure of the lamprey yolk lipid-protein complex lipovitellin-phosvitin at 2.8 A resolution. J Mol Biol 200(3):553–569PubMedCrossRefGoogle Scholar
  35. 35.
    Rina M, Savakis C (1991) A cluster of vitellogenin genes in the Mediterranean fruit fly Ceratitis capitata: sequence and structural conservation in dipteran yolk proteins and their genes. Genetics 127(4):769–780PubMedGoogle Scholar
  36. 36.
    Seehuus SC, Norberg K, Gimsa U, Krekling T, Amdam GV (2006) Reproductive protein protects sterile honey bee workers from oxidative stress. Proc Natl Acad Sci USA 103:962–967PubMedCrossRefGoogle Scholar
  37. 37.
    Seeley TD (1995) The wisdom of the hive. Harvard University Press, CambridgeGoogle Scholar
  38. 38.
    Slessor KN, Winston ML, Le Conte Y (2005) Pheromone communication in the honeybee (Apis mellifera L.). J Chem Ecol 31(11):2731–2745PubMedCrossRefGoogle Scholar
  39. 39.
    Snodgrass RE (1956) Anatomy of the honey bee. Comstock, New YorkGoogle Scholar
  40. 40.
    Stay B, Zera AJ (2010) Morph-specific diurnal variation in allatostatin immunostaining in the corpora allata of Gryllus firmus: implications for the regulation of a morph-specific circadian rhythm for JH biosynthetic rate. J Insect Physiol 56(3):266–270PubMedCrossRefGoogle Scholar
  41. 41.
    Tatar M, Bartke A, Antebi A (2003) The endocrine regulation of aging by insulin-like signals. Science 299:1346–1350PubMedCrossRefGoogle Scholar
  42. 42.
    Tufail M, Takeda M (2008) Molecular characteristics of insect vitellogenins. J Insect Physiol 54(12):1447–1458PubMedCrossRefGoogle Scholar
  43. 43.
    Wahli W, Dawid IB (1980) Isolation of two closely related vitellogenin genes, including their flanking regions, from a Xenopus laevis gene library. Proc Natl Acad Sci USA 77(3):1437–1441PubMedCrossRefGoogle Scholar
  44. 44.
    Walter J, Schindzielorz A, Grünberg J, Haass C (1999) Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis. Proc Natl Acad Sci USA 96(4):1391–1396PubMedCrossRefGoogle Scholar
  45. 45.
    Weinstock GM, Robinson GE, Gibbs RA, Weinstock GM, Weinstock GM et al (2006) Insights into social insects from the genome of the honeybee Apis mellifera. Nature 443(7114):931–949CrossRefGoogle Scholar
  46. 46.
    Wheeler DE, Kawooya JK (1990) Purification and characterization of honey bee vitellogenin. Arch Insect Biochem Physiol 14:253–267PubMedCrossRefGoogle Scholar
  47. 47.
    Williams SL, Essex JW (2009) Study of the conformational dynamics of the catalytic loop of WT and G140A/G149A HIV-1 Integrase core domain using reversible digitally filtered molecular dynamics. J Chem Theor Comp 5:411–421CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.School of Life SciencesArizona State UniversityTempeUSA
  2. 2.Department of Chemistry, Biotechnology and Food ScienceNorwegian University of Life SciencesAasNorway

Personalised recommendations