Skip to main content
SpringerLink
Log in

Myoinhibiting peptides are the ancestral ligands of the promiscuous Drosophila sex peptide receptor

  • Research Article
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Male insects change behaviors of female partners by co-transferring accessory gland proteins (Acps) like sex peptide (SP), with their sperm. The Drosophila sex peptide receptor (SPR) is a G protein-coupled receptor expressed in the female’s nervous system and genital tract. While most Acps show a fast rate of evolution, SPRs are highly conserved in insects. We report activation of SPRs by evolutionary conserved myoinhibiting peptides (MIPs). Structural determinants in SP and MIPs responsible for this dual receptor activation are characterized. Drosophila SPR is also expressed in embryonic and larval stages and in the adult male nervous system, whereas SP expression is restricted to the male reproductive system. MIP transcripts occur in male and female central nervous system, possibly acting as endogenous SPR ligands. Evolutionary consequences of the promiscuous nature of SPRs are discussed. MIPs likely function as ancestral ligands of SPRs and could place evolutionary constraints on the MIP/SPR class.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Abbreviations

Acps:

Accessory gland proteins

CNS:

Central nervous system

GPCR:

G protein-coupled receptor

MIP:

Myoinhibiting peptide

SP:

Sex peptide

SPR:

Sex peptide receptor

References

  1. Schoofs L, Holman GM, Hayes TK, Nachman RJ, De Loof A (1991) Isolation, identification and synthesis of locustamyoinhibiting peptide (LOM-MIP), a novel biologically active neuropeptide from Locusta migratoria. Regul Pept 36:111–119

    Article  CAS  PubMed  Google Scholar 

  2. Blackburn MB, Wagner RM, Kochansky JP, Harrison DJ, Thomaslaemont P, Raina AK (1995) The identification of 2 myoinhibitory peptides, with sequence similarities to the galanins, isolated from the ventral nerve cord of Manduca sexta. Regul Pept 57:213–219

    Article  CAS  PubMed  Google Scholar 

  3. Lorenz MW, Kellner R, Hoffmann KH (1995) A family of neuropeptides that inhibit juvenile hormone biosynthesis in the cricket, Gryllus bimaculatus. J Biol Chem 270:21103–21108

    Article  CAS  PubMed  Google Scholar 

  4. Hua YJ, Tanaka Y, Nakamura K, Sakakibara M, Nagata S, Kataoka H (1999) Identification of a prothoracicostatic peptide in the larval brain of the silkworm, Bombyx mori. J Biol Chem 274:31169–31173

    Article  CAS  PubMed  Google Scholar 

  5. Vanden Broeck J (2001) Neuropeptides and their precursors in the fruitfly, Drosophila melanogaster. Peptides 22:241–254

    Article  Google Scholar 

  6. Williamson M, Lenz C, Winther ME, Nassel DR, Grimmelikhuijzen CJP (2001) Molecular cloning, genomic organization, and expression of a B-type (cricket-type) allatostatin preprohormone from Drosophila melanogaster. Biochem Biophys Res Commun 281:544–550

    Article  CAS  PubMed  Google Scholar 

  7. Predel R, Wegener C, Russell WK, Tichy SE, Russell DH, Nachman RJ (2004) Peptidomics of CNS-associated neurohemal systems of adult Drosophila melanogaster: a mass spectrometric survey of peptides from individual flies. J Comp Neurol 474:379–392

    Article  CAS  PubMed  Google Scholar 

  8. Baggerman G, Boonen K, Verleyen P, De Loof A, Schoofs L (2005) Peptidomic analysis of the larval Drosophila melanogaster central nervous system by two-dimensional capillary liquid chromatography quadrupole time-of-flight mass spectrometry. J Mass Spectrom 40:250–260

    Article  CAS  PubMed  Google Scholar 

  9. Yapici N, Kim YJ, Ribeiro C, Dickson BJ (2008) A receptor that mediates the post-mating switch in Drosophila reproductive behaviour. Nature 451:33–37

    Article  PubMed  Google Scholar 

  10. Chen PS, Stumm-Zollinger E, Aigaki T, Balmer J, Bienz M, Bohlen P (1988) A male accessory gland peptide that regulates reproductive behavior of female D. melanogaster. Cell 54:291–298

    Article  CAS  PubMed  Google Scholar 

  11. Chapman T, Liddle LF, Kalb JM, Wolfner MF, Partridge L (1995) Cost of mating in Drosophila melanogaster females is mediated by male accessory-gland products. Nature 373:241–244

    Article  CAS  PubMed  Google Scholar 

  12. Peng J, Zipperlen P, Kubli E (2005) Drosophila sex-peptide stimulates female innate immune system after mating via the Toll and Imd pathways. Curr Biol 15:1690–1694

    Article  CAS  PubMed  Google Scholar 

  13. Wigby S, Chapman T (2005) Sex peptide causes mating costs in female Drosophila melanogaster. Curr Biol 15:316–321

    Article  CAS  PubMed  Google Scholar 

  14. Carvalho GB, Kapahi P, Anderson DJ, Benzer S (2006) Allocrine modulation of feeding behavior by the sex peptide of Drosophila. Curr Biol 16:692–696

    Article  CAS  PubMed  Google Scholar 

  15. Domanitskaya EV, Liu HF, Chen SJ, Kubli E (2007) The hydroxyproline motif of male sex peptide elicits the innate immune response in Drosophila females. FEBS J 274:5659–5668

    Article  CAS  PubMed  Google Scholar 

  16. Hasemeyer M, Yapici N, Heberlein U, Dickson BJ (2009) Sensory neurons in the Drosophila genital tract regulate female reproductive behavior. Neuron 61:511–518

    Article  PubMed  Google Scholar 

  17. Yang CH, Rumpf S, Xiang Y, Gordon MD, Song W, Jan LY, Jan YN (2009) Control of the postmating behavioral switch in Drosophila females by internal sensory neurons. Neuron 61:519–526

    Article  CAS  PubMed  Google Scholar 

  18. Kubli E (2003) Sex-peptides: seminal peptides of the Drosophila male. Cell Mol Life Sci 60:1689–1704

    Article  CAS  PubMed  Google Scholar 

  19. Wigby S, Sirot LK, Linklater JR, Buehner N, Calboli FC, Bretman A, Wolfner MF, Chapman T (2009) Seminal fluid protein allocation and male reproductive success. Curr Biol 19:751–757

    Article  CAS  PubMed  Google Scholar 

  20. Schmidt T, Choffat Y, Schneider M, Hunziker P, Fuyama Y, Kubli E (1993) Drosophila suzukii contains a peptide homologous to the Drosophila melanogaster sex-peptide and functional in both species. Insect Biochem Mol Biol 23:571–579

    Article  CAS  PubMed  Google Scholar 

  21. Cirera S, Aguade M (1998) Molecular evolution of a duplication: the sex-peptide (Acp70A) gene region of Drosophila subobscura and Drosophila madeirensis. Mol Biol Evol 15:988–996

    CAS  PubMed  Google Scholar 

  22. Nagalakshmi VK, Applebaum SW, Azrielli A, Rafaeli A (2007) Female sex pheromone suppression and the fate of sex-peptide-like peptides in mated moths of Helicoverpa armigera. Arch Insect Biochem Physiol 64:142–155

    Article  CAS  PubMed  Google Scholar 

  23. Knight PJK, Pfeifer TA, Grigliatti TA (2003) A functional assay for G-protein-coupled receptors using stably transformed insect tissue culture cell lines. Anal Biochem 320:88–103

    Article  CAS  PubMed  Google Scholar 

  24. Le Poul E, Hisada S, Mizuguchi Y, Dupriez VJ, Burgeon E, Detheux M (2002) Adaptation of aequorin functional assay to high throughput screening. J Biomol Screen 7:57–65

    Article  CAS  PubMed  Google Scholar 

  25. Chapman T, Choffat Y, Lucas WE, Kubli E, Partridge L (1996) Lack of response to sex-peptide results in increased cost of mating in dunce Drosophila melanogaster females. J Insect Physiol 42:1007–1015

    Article  CAS  Google Scholar 

  26. Rovati GE, Capra V, Neubig RR (2007) The highly conserved DRY motif of class A G protein-coupled receptors: beyond the ground state. Mol Pharmacol 71:959–964

    Article  CAS  PubMed  Google Scholar 

  27. Schmidt T, Choffat Y, Klauser S, Kubli E (1993) The Drosophila melanogaster sex peptide—a molecular analysis of structure-function relationships. J Insect Physiol 39:361–368

    Article  CAS  Google Scholar 

  28. Saudan P, Hauck K, Soller M, Choffat Y, Ottiger M, Sporri M, Ding ZB, Hess D, Gehrig PM, Klauser S, Hunziker P, Kubli E (2002) Ductus ejaculatorius peptide 99B (DUP99B), a novel Drosophila melanogaster sex-peptide pheromone. Eur J Biochem 269:989–997

    Article  CAS  PubMed  Google Scholar 

  29. Ding ZB, Haussmann I, Ottiger M, Kubli E (2003) Sex-peptides bind to two molecularly different targets in Drosophila melanogaster females. J Neurobiol 55:372–384

    Article  CAS  PubMed  Google Scholar 

  30. Peng J, Chen S, Busser S, Liu HF, Honegger T, Kubli E (2005) Gradual release of sperm bound sex-peptide controls female postmating behavior in Drosophila. Curr Biol 15:207–213

    Article  CAS  PubMed  Google Scholar 

  31. Johnson EC, Bohn LM, Barak LS, Birse RT, Nässel DR, Caron MG, Taghert PH (2003) Identification of Drosophila neuropeptide receptors by G protein-coupled receptors-beta-arrestin2 interactions. J Biol Chem 278:52172–52178

    Article  CAS  PubMed  Google Scholar 

  32. Poels J, Birse RT, Nachman RJ, Fichna J, Janecka A, Vanden Broeck J, Nässel DR (2009) Characterization and distribution of NKD, a receptor for Drosophila tachykinin-related peptide 6. Peptides 30:545–556

    Article  CAS  PubMed  Google Scholar 

  33. Ja WW, Carvalho GB, Madrigal M, Roberts RW, Benzer S (2009) The Drosophila G protein-coupled receptor, Methuselah, exhibits a promiscuous response to peptides. Protein Sci 18:2203–2208

    Article  CAS  PubMed  Google Scholar 

  34. Birse RT, Johnson EC, Taghert PH, Nässel DR (2006) Widely distributed Drosophila G-protein-coupled receptor (CG7887) is activated by endogenous tachykinin-related peptides. J Neurobiol 66:33–46

    Article  CAS  PubMed  Google Scholar 

  35. Schoofs L, Veelaert D, Vanden Broeck J, De Loof A (1996) Immunocytochemical distribution of locustamyoinhibiting peptide (Lom-MIP) in the nervous system of Locusta migratoria. Regul Pept 63:171–179

    CAS  PubMed  Google Scholar 

  36. Kim YJ, Zitnan D, Cho KH, Schooley DA, Mizoguchi A, Adams ME (2006) Central peptidergic ensembles associated with organization of an innate behavior. Proc Natl Acad Sci USA 103:14211–14216

    Article  CAS  PubMed  Google Scholar 

  37. Kim YJ, Zitnan D, Galizia CG, Cho KH, Adams ME (2006) A command chemical triggers an innate behavior by sequential activation of multiple peptidergic ensembles. Curr Biol 16:1395–1407

    Article  CAS  PubMed  Google Scholar 

  38. Aigaki T, Fleischmann I, Chen PS, Kubli E (1991) Ectopic expression of sex peptide alters reproductive behavior of female Drosophila melanogaster. Neuron 7:557–563

    Article  CAS  PubMed  Google Scholar 

  39. Liu HF, Kubli E (2003) Sex-peptide is the molecular basis of the sperm effect in Drosophila melanogaster. Proc Natl Acad Sci USA 100:9929–9933

    Article  CAS  PubMed  Google Scholar 

  40. Swanson WJ (2003) Sex peptide and the sperm effect in Drosophila melanogaster. Proc Natl Acad Sci USA 100:9643–9644

    Article  CAS  PubMed  Google Scholar 

  41. Yamanaka N, Hua YJ, Roller L, Spalovska-Valachova I, Mizoguchi A, Kataoka H, Tanaka Y (2010) Bombyx prothoracicostatic peptides activate the sex peptide receptor to regulate ecdysteroid biosynthesis. Proc Natl Acad Sci USA 107:2060–2065

    Article  CAS  PubMed  Google Scholar 

  42. Harshman LG, Loeb AM, Johnson BA (1999) Ecdysteroid titers in mated and unmated Drosophila melanogaster females. J Insect Physiol 45:571–577

    Article  CAS  PubMed  Google Scholar 

  43. Aguade M (1999) Positive selection drives the evolution of the Acp29AB accessory gland protein in Drosophila. Genetics 152:543–551

    CAS  PubMed  Google Scholar 

  44. Begun DJ, Whitley P, Todd BL, Waldrip-Dail HM, Clark AG (2000) Molecular population genetics of male accessory gland proteins in Drosophila. Genetics 156:1879–1888

    CAS  PubMed  Google Scholar 

  45. Swanson WJ, Clark AG, Waldrip-Dail HM, Wolfner MF, Aquadro CF (2001) Evolutionary EST analysis identifies rapidly evolving male reproductive proteins in Drosophila. Proc Natl Acad Sci USA 98:7375–7379

    Article  CAS  PubMed  Google Scholar 

  46. Andres JA, Maroja LS, Bogdanowicz SM, Swanson WJ, Harrison RG (2006) Molecular evolution of seminal proteins in field crickets. Mol Biol Evol 23:1574–1584

    Article  CAS  PubMed  Google Scholar 

  47. Haerty W, Jagadeeshan S, Kulathinal RJ, Wong A, Ram KR, Sirot LK, Levesque L, Artieri CG, Wolfner MF, Civetta A, Singh RS (2007) Evolution in the fast lane: rapidly evolving sex-related genes in Drosophila. Genetics 177:1321–1335

    Article  CAS  PubMed  Google Scholar 

  48. Rice WR (1996) Sexually antagonistic male adaptation triggered by experimental arrest of female evolution. Nature 381:232–234

    Article  CAS  PubMed  Google Scholar 

  49. Rice WR, Stewart AD, Morrow EH, Linder JE, Orteiza N, Byrne PG (2006) Assessing sexual conflict in the Drosophila melanogaster laboratory model system. Philos Trans R Soc Lond B Biol Sci 361:287–299

    Article  PubMed  Google Scholar 

  50. Singh RS, Kulathinal RJ (2005) Male sex drive and the masculinization of the genome. Bioessays 27:518–525

    Article  CAS  PubMed  Google Scholar 

  51. Barnes AI, Wigby S, Boone JM, Partridge L, Chapman T (2008) Feeding, fecundity and lifespan in female Drosophila melanogaster. Proc Biol Sci 275:1675–1683

    Article  PubMed  Google Scholar 

  52. Fricke C, Bretman A, Chapman T (2010) Female nutritional status determines the magnitude and sign of responses to a male ejaculate signal in Drosophila melanogaster. J Evol Biol 23:157–165

    Article  CAS  PubMed  Google Scholar 

  53. Linder JE, Rice WR (2005) Natural selection and genetic variation for female resistance to harm from males. J Evol Biol 18:568–575

    Article  CAS  PubMed  Google Scholar 

  54. Chapman T (2006) Evolutionary conflicts of interest between males and females. Curr Biol 16:R744–R754

    Article  CAS  PubMed  Google Scholar 

  55. Dottorini T, Nicolaides L, Ranson H, Rogers DW, Crisanti A, Catteruccia F (2007) A genome-wide analysis in Anopheles gambiae mosquitoes reveals 46 male accessory gland genes, possible modulators of female behavior. Proc Natl Acad Sci USA 104:16215–16220

    Article  CAS  PubMed  Google Scholar 

  56. Kubli E (2008) Sexual behaviour: a receptor for sex control in Drosophila females. Curr Biol 18:R210–R212

    Article  CAS  PubMed  Google Scholar 

  57. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23:2947–2948

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank L. Vanden Bosch and J. Van Duppen for technical support, B. Breugelmans and V. van Hoef for supplying Bombyx and Tribolium cDNA, and M. Parmentier (University of Brussels, Belgium) and M. Detheux (Euroscreen S.A., Belgium) for providing WTA11 cells. The authors gratefully acknowledge the Interuniversity Attraction Poles program (Belgian Science Policy Grant P6/14), the Research Foundation of Flanders (FWO-Flanders), the K.U. Leuven Research Foundation (GOA 2005/06) and the USDA/DOD DWFP Initiative (#0500-32000-001-01R) (R.J.N). B.V.H. was supported by the IWT and J.P. obtained a postdoctoral research fellowship from FWO.

Author information

Authors and Affiliations

  1. Animal Physiology and Neurobiology, Katholieke Universiteit Leuven, Naamsestraat 59, 3000, Leuven, Belgium

    Jeroen Poels, Tom Van Loy, Hans Peter Vandersmissen, Boris Van Hiel, Sofie Van Soest & Jozef Vanden Broeck

  2. Areawide Pest Management Research, Southern Plains Agricultural Research Center, College Station, TX, 77845, USA

    Ronald J. Nachman

Authors
  1. Jeroen Poels
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tom Van Loy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hans Peter Vandersmissen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Boris Van Hiel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sofie Van Soest
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ronald J. Nachman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jozef Vanden Broeck
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeroen Poels.

Additional information

J. Poels and T. Van Loy have equally contributed to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Poels, J., Van Loy, T., Vandersmissen, H.P. et al. Myoinhibiting peptides are the ancestral ligands of the promiscuous Drosophila sex peptide receptor. Cell. Mol. Life Sci. 67, 3511–3522 (2010). https://doi.org/10.1007/s00018-010-0393-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-010-0393-8

Keywords

Search

Navigation