Skip to main content
Log in

Insertion Mutations of the shaggy Gene, Encoding Protein Kinase GSK3, Extend Drosophila melanogaster Lifespan

  • SHORT COMMUNICATIONS
  • Published:
Russian Journal of Genetics Aims and scope Submit manuscript

Abstract

The shaggy gene of Drosophila melanogaster encodes highly conserved serine-threonine protein kinase GSK3 (Glycogen Syntase Kinase 3), which plays an important role in different signaling pathways and metabolic processes. This study is the first to demonstrate that shaggy mutations affect lifespan, with an increase in longevity associated with a decrease in synapse activity. The results from this study on changes in shaggy expression in mutants suggest that the observed phenotypic changes are based on an alternation in the expression of minor shaggy transcripts induced by mutational changes in their regulatory region.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1.

Similar content being viewed by others

REFERENCES

  1. Colosimo, P.F., Liu, X., Kaplan, N.A., and Tolwinski, N.S., GSK3beta affects apical-basal polarity and cell—cell adhesion by regulating aPKC levels, Dev. Dyn., 2010, vol. 239, pp. 115—125. https://doi.org/10.1002/dvdy.21963

    Article  CAS  PubMed  Google Scholar 

  2. Pasyukova, E.G., Symonenko, A.V., Roshina, N.V., et al., Neuronal genes and developmental neuronal pathways in Drosophila lifespan control, in Life Extension, Healthy Ageing and Longevity, 3: Life Extension: Lessons from Drosophila, Springer-Verlag, 2015, pp. 3—37. https://doi.org/10.1007/978-3-319-18326-8_1.

  3. Symonenko, A.V., Roshina, N.V., Krementsova, A.V., and Pasyukova, E.G., Reduced neuronal transcription of escargot, the Drosophila gene encoding a Snail-type transcription factor, promotes longevity, Front. Genet., 2018, vol. 9, p. 151. https://doi.org/10.3389/fgene.2018.00151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. McGraw, E.A. and O’Neill, S.L., Wolbachia pipientis: intracellular infection and pathogenesis in Drosophila, Curr. Opin. Microbiol., 2004, vol. 7, pp. 67—70. https://doi.org/10.1016/j.mib.2003.12.003

    Article  CAS  PubMed  Google Scholar 

  5. Wilmoth, J.R. and Horiuchi, S., Rectangularization revisited: variability of age at death within human populations, Demography, 1999, vol. 36, pp. 475—495.

    Article  CAS  Google Scholar 

  6. Carey, J.R., Longevity: the Biology and Demography of Life Span, Princeton: Princeton Univ. Press, 2003.

    Google Scholar 

  7. Tower, J., Sex-specific gene expression and life span regulation, Trends Endocrinol. Metab., 2017, vol. 28, pp. 735—747. https://doi.org/10.1016/j.tem.2017.07.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Franciscovich, A.L., Mortimer, A.D., Freeman, A.A., et al., Overexpression screen in Drosophila identifies neuronal roles of GSK-3 beta/shaggy as a regulator of AP-1-dependent developmental plasticity, Genetics, 2008, vol. 180, pp. 2057—2071. https://doi.org/10.1534/genetics.107.085555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ruiz-Canada, C. and Budnik, V., Introduction on the use of the Drosophila embryonic/larval neuromuscular junction as a model system to study synapse development and function, and a brief summary of pathfinding and target recognition, Int. Rev. Neurobiol., 2006, vol. 75, pp. 1—31. https://doi.org/10.1016/S0074-7742(06)75001-2

    Article  CAS  PubMed  Google Scholar 

  10. Rybina, O.Y., Sarantseva, S.V., Veselkina, E.R., et al., Tissue-specific transcription of the neuronal gene Lim3 affects Drosophila melanogaster lifespan and locomotion, Biogerontology, 2017, vol. 18, pp. 739—757. https://doi.org/10.1007/s10522-017-9704-x

    Article  CAS  PubMed  Google Scholar 

  11. Wagh, D.A., Rasse, T.M., Asan, E., et al., Bruchpilot, a protein with homology to ELKS/CAST, is required for structural integrity and function of synaptic active zones in Drosophila, Neuron, 2006, vol. 49, pp. 833—448. https://doi.org/10.1016/j.neuron.2006.02.008

    Article  CAS  PubMed  Google Scholar 

  12. Franco, B., Bogdanik, L., Bobinnec, Y., et al., Shaggy, the homolog of glycogen synthase kinase 3, controls neuromuscular junction growth in Drosophila, J. Neurosci., 2004, vol. 24, pp. 6573—6577. https://doi.org/10.1523/JNEUROSCI.1580-04.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ruel, L., Pantesco, V., Lutz, Y., et al., Functional significance of a family of protein kinases encoded at the shaggy locus in Drosophila, EMBO J., 1993, vol. 12, pp. 1657—1669.

    Article  CAS  Google Scholar 

  14. Bourouis, M., Targeted increase in shaggy activity levels blocks Wingless signaling, Genesis, 2002, vol. 34, pp. 99—102. https://doi.org/10.1002/gene.10114

    Article  CAS  PubMed  Google Scholar 

  15. Brunner, E., Ahrens, C.H., Mohanty, S., et al., A high-quality catalog of the Drosophila melanogaster proteome, Nat. Biotechnol., 2007, vol. 25, pp. 576—583. https://doi.org/10.1038/nbt1300

    Article  CAS  PubMed  Google Scholar 

  16. Tress, M.L., Bodenmiller, B., Aebersold, R., and Valencia, A., Proteomics studies confirm the presence of alternative protein isoforms on a large scale, Genome Biol., 2008, vol. 9, R162. https://doi.org/10.1186/gb-2008-9-11-r162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pritschet, L., Powell, D., and Horne, Z., Marginally significant effects as evidence for hypotheses: changing attitudes over four decades, Psychol. Sci., 2016, vol. 27, pp. 1036—1042. https://doi.org/10.1177/0956797616645672

    Article  PubMed  Google Scholar 

  18. Brand, A.H. and Perrimon, N., Targeted gene expression as a means of altering cell fates and generating dominant phenotypes, Development, 1993, vol. 118, pp. 401—415.

    CAS  PubMed  Google Scholar 

Download references

ACKNOWLEDGMENTS

We thank L.V. Olenina for consultations and discussion of the study. We are grateful to the staff of the Bloomington Drosophila Stock Center (Bloomington, USA, https:// bdsc.indiana.edu/index.html) for many years of assistance to our research.

This study was carried out using the equipment of the Shared Research Center of the Institute of Molecular Genetics of the Russian Academy of Sciences.

Funding

This study was supported by the state contract with the Institute of Molecular Genetics of the Russian Academy of Sciences (state registration no. AAAA-A19-119022590053-3) and by the Russian Foundation for Basic Research (grant nos. 18-34-00934-mol_a, 19-34-80042-mol_ev_a).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E. G. Pasyukova.

Ethics declarations

Statement on the welfare of animals. This article does not contain any research using vertebrate animals as subject.

Statement of compliance with standards of research involving humans as subjects. This article does not contain any research involving humans as subject.

Conflicts of interest. The authors declare that they have no conflicts of interest.

Additional information

Translated by N. Maleeva

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Trostnikov, M.V., Veselkina, E.R., Krementsova, A.V. et al. Insertion Mutations of the shaggy Gene, Encoding Protein Kinase GSK3, Extend Drosophila melanogaster Lifespan. Russ J Genet 55, 1165–1170 (2019). https://doi.org/10.1134/S1022795419090163

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1022795419090163

Keywords:

Navigation