Overexpression of isoform B of Dgp-1 gene enhances locomotor activity in senescent Drosophila males and under heat stress

  • Sergey A. FedotovEmail author
  • Natalia G. Besedina
  • Julia V. Bragina
  • Larisa V. Danilenkova
  • Elena A. Kamysheva
  • Nikolai G. Kamyshev
Original Paper


Here, we describe the longevity and locomotor behavior of senescent Drosophila males with altered expression of Dgp-1 gene. In comparison with the wild-type Canton-S (CS) males, six characteristics of the phenotype of Dgp-1[843k] mutant were found: (1) low expression of isoform A; (2) augmented expression of isoform B; (3) reduction in the mean lifespan; (4) decrease in the running speed in 3-day-old flies; (5) maintenance of a high run frequency in senescent flies; and (6) resistance to heat stress manifested as maintenance of a high run frequency at 29 °C. After cessation of “cantonization” process, mean lifespan of the mutant males drifted from low to high values finally exceeding that for CS. In contrast, behavioral phenotype of the mutant was robust. Using the GAL4/UAS system, we showed that neurospecific overexpression of isoform B resulted in a slight decrease of longevity and a high level of run frequency in the senescent flies, similar to that in Dgp-1[843K] mutant. In addition, a decreased level of reactive oxygen species was found in Dgp-1[843K] mutant males maintained under stress conditions. The elevated resistance to oxidative stress probably explains the two distinctive features of the mutation: resistance to aging processes and thermal stress displayed at behavioral level.


Locomotion Heat stress Senescence Oxidative stress Drosophila Dgp-1 mutant 



Age-related locomotor impairments


Confidence intervals




Genome-wide association study


Insulin/insulin-like growth factor signaling


Reactive oxygen species



We thank the Bloomington Drosophila Stock Center at Indiana University (USA) and the Vienna Drosophila Resource Center at Campus Science Support Facilities (Austria) for providing us with transgenic GAL4 and RNAi fly stocks. We are grateful to Dr. Konstantin G. Iliadi (The Hospital for Sick Children, Toronto, ON, Canada) for propagation, maintenance, and transcontinental shipment of these stocks to our laboratory. In addition, our gratitude is to Center “Biocollection” at Pavlov Institute of Physiology for help in the maintenance of Drosophila lines. Many thanks to anonymous reviewer who prompted us to consider sleep as a possible target of Dgp-1[843K] mutation and corrected our English language in the first version of the manuscript.


This work was supported by the project Mega_SPbU_2013—6 from St. Petersburg State University, the Postdoctoral fellowship program (ID = 34799261) of personnel support for research conducted under the guidance of leading scientists of St. Petersburg State University, the Russian Program of fundamental researches (2013–2020, GP-14, section 63). The funding sources had no involvement in any aspects of the study.

Compliance with ethical standards

Conflict of interest

Sergey A. Fedotov, Natalia G. Besedina, Julia V. Bragina, Larisa V. Danilenkova, Elena A. Kamysheva, and Nikolai G. Kamyshev declare that they have no conflict of interest.

Research involving human participants and/or animals

This article does not contain any studies with human participants or vertebrates performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.


  1. Abbas N, Lücking CB, Ricard S, Dürr A, Bonifati V, De Michele G, Bouley S, Vaughan JR, Gasser T, Marconi R, Broussolle E, Brefel-Courbon C, Harhangi BS, Oostra BA, Fabrizio E, Böhme GA, Pradier L, Wood NW, Filla A, Meco G, Denefle P, Agid Y, Brice A (1999) A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. Hum Mol Genet 8:567–574CrossRefGoogle Scholar
  2. Agrawal N, Delanoue R, Mauri A, Basco D, Pasco M, Thorens B, Léopold P (2016) The Drosophila TNF Eiger is an adipokine that acts on insulin-producing cells to mediate nutrient response. Cell Metab 23:675–684. CrossRefPubMedGoogle Scholar
  3. Augustin H, McGourty K, Allen MJ, Madem SK, Adcott J, Kerr F, Wong CT, Vincent A, Godenschwege T, Boucrot E, Partridge L (2017) Reduced insulin signaling maintains electrical transmission in a neural circuit in aging flies. PLoS Biol 15:e2001655. CrossRefPubMedPubMedCentralGoogle Scholar
  4. Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120:483–495. CrossRefPubMedGoogle Scholar
  5. Bushey D, Hughes KA, Tononi G, Cirelli C (2010) Sleep, aging, and lifespan in Drosophila. BMC Neurosci 11:56. CrossRefPubMedPubMedCentralGoogle Scholar
  6. Danilov A, Shaposhnikov M, Shevchenko O, Zemskaya N, Zhavoronkov A, Moskalev A (2015) Influence of non-steroidal anti-inflammatory drugs on Drosophila melanogaster longevity. Oncotarget 6:19428–19444. CrossRefPubMedPubMedCentralGoogle Scholar
  7. de Belle JS, Heisenberg M (1996) Expression of Drosophila mushroom body mutations in alternative genetic backgrounds: a case study of the mushroom body miniature gene (mbm). Proc Natl Acad Sci U S A 93:9875–9880CrossRefGoogle Scholar
  8. Donelson NC, Kim EZ, Slawson JB, Vecsey CG, Huber R, Griffith LC (2012) High-resolution positional tracking for long-term analysis of Drosophila sleep and locomotion using the “tracker” program. PLoS One. 7:e37250. CrossRefPubMedPubMedCentralGoogle Scholar
  9. Edgington ES (1995) Randomization tests. Marcel Dekker, New YorkGoogle Scholar
  10. Efron B, Tibshirani RJ (1993) An introduction to the bootstrap. Chapman and Hall, LondonCrossRefGoogle Scholar
  11. Fedotov SA, Bragina JV, Besedina NG, Danilenkova LV, Kamysheva EA, Panova AA, Kamyshev NG (2014) The effect of neurospecific knockdown of candidate genes for locomotor behavior and sound production in Drosophila melanogaster. Fly 8:176–187. CrossRefPubMedPubMedCentralGoogle Scholar
  12. Fedotov SA, Bragina JV, Besedina NG, Danilenkova LV, Kamysheva EA, Kamyshev NG (2018) Gene CG15630 (fipi) is involved in regulation of the interpulse interval in Drosophila courtship song. J Neurogenet 32:15–26. CrossRefPubMedGoogle Scholar
  13. Gaitanidis A, Dimitriadou A, Dowse H, Sanyal S, Duch C, Consoulas C (2019) Longitudinal assessment of health-span and pre-death morbidity in wild type Drosophila. Aging (Albany NY) 11:1850–1873. CrossRefGoogle Scholar
  14. Girardot F, Monnier V, Tricoire H (2004) Genome wide analysis of common and specific stress responses in adult drosophila melanogaster. BMC Genom 5:74. CrossRefGoogle Scholar
  15. Greene JC, Whitworth AJ, Andrews LA, Parker TJ, Pallanck LJ (2005) Genetic and genomic studies of Drosophila parkin mutants implicate oxidative stress and innate immune responses in pathogenesis. Hum Mol Genet 14:799–811. CrossRefPubMedGoogle Scholar
  16. Gruenewald C, Botella JA, Bayersdorfer F, Navarro JA, Schneuwly S (2009) Hyperoxia-induced neurodegeneration as a tool to identify neuroprotective genes in Drosophila melanogaster. Free Radic Biol Med 46:1668–1676. CrossRefPubMedGoogle Scholar
  17. Ismail MZBH, Hodges MD, Boylan M, Achall R, Shirras A, Broughton SJ (2015) The Drosophila insulin receptor independently modulates lifespan and locomotor senescence. PLoS One 10:e0125312. CrossRefPubMedPubMedCentralGoogle Scholar
  18. Jia FX, Dou W, Hu F, Wang J-J (2011) Effects of thermal stress on lipid peroxidation and antioxidant enzyme activities of oriental fruit fly, Bactrocera dorsalis (Diptera: Tephritidae). Fla Entomol 94:956–963CrossRefGoogle Scholar
  19. Jones MA, Grotewiel M (2011) Drosophila as a model for age-related impairment in locomotor and other behaviors. Exp Gerontol 46:320–325. CrossRefPubMedGoogle Scholar
  20. Jordan KW, Craver KL, Magwire MM, Cubilla CE, Mackay TF, Anholt RR (2012) Genome-wide association for sensitivity to chronic oxidative stress in Drosophila melanogaster. PLoS One 7:e38722. CrossRefPubMedPubMedCentralGoogle Scholar
  21. Landis G, Bhole D, Lu L, Tower J (2001) High-frequency generation of conditional mutations affecting Drosophila melanogaster development and life span. Genetics 158:1167–1176PubMedPubMedCentralGoogle Scholar
  22. Lavara-Culebras E, Muñoz-Soriano V, Gómez-Pastor R, Matallana E, Paricio N (2010) Effects of pharmacological agents on the lifespan phenotype of Drosophila DJ-1beta mutants. Gene 462:26–33. CrossRefPubMedGoogle Scholar
  23. LeBel CP, Ischiropoulos H, Bondy SC (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5:227–231CrossRefGoogle Scholar
  24. Nasiri Moghadam N, Holmstrup M, Manenti T, Brandt Mouridsen M, Pertoldi C, Loeschcke V (2015) The role of storage lipids in the relation between fecundity, locomotor activity, and lifespan of Drosophila melanogaster longevity-selected and control lines. PLoS One 10:e0130334. CrossRefPubMedPubMedCentralGoogle Scholar
  25. Nègre N, Brown CD, Shah PK, Kheradpour P, Morrison CA, Henikoff JG, Feng X, Ahmad K, Russell S, White RA, Stein L, Henikoff S, Kellis M, White KP (2010) A comprehensive map of insulator elements for the Drosophila genome. PLoS Genet 6:e1000814. CrossRefPubMedPubMedCentralGoogle Scholar
  26. Panova AA, Bragina JV, Danilenkova LV, Besedina NG, Kamysheva EA, Fedotov SA, Kamyshev NG (2013) Group rearing leads to long-term changes in locomotor activity of Drosophila males. Open J Animal Sci 3:31–35. CrossRefGoogle Scholar
  27. Parameswaran N, Patial S (2010) Tumor necrosis factor-α signaling in macrophages. Crit Rev Eukaryot Gene Expr 20:87–103CrossRefGoogle Scholar
  28. Parisky KM, Agosto Rivera JL, Donelson NC, Kotecha S, Griffith LC (2016) Reorganization of sleep by temperature in Drosophila requires light, the homeostat, and the circadian clock. Curr Biol 26:882–892. CrossRefPubMedPubMedCentralGoogle Scholar
  29. Park J, Kim SY, Cha G-H, Lee SB, Kim S, Chung J (2005) Drosophila DJ-1 mutants show oxidative stress-sensitive locomotive dysfunction. Gene 361:133–139. CrossRefPubMedGoogle Scholar
  30. Petrosyan A, Gonçalves ÓF, Hsieh I-H, Saberi K (2014) Improved functional abilities of the life-extended Drosophila mutant Methuselah are reversed at old age to below control levels. Age 36:213–221. CrossRefPubMedGoogle Scholar
  31. Pfaffl MW, Horgan GW, Dempfle L (2002) Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30:e36CrossRefGoogle Scholar
  32. Rhodenizer D, Martin I, Bhandari P, Pletcher SD, Grotewiel M (2008) Genetic and environmental factors impact age-related impairment of negative geotaxis in Drosophila by altering age-dependent climbing speed. Exp Gerontol 43:739–748. CrossRefPubMedPubMedCentralGoogle Scholar
  33. Senju S, Iyama K, Kudo H, Aizawa S, Nishimura Y (2000) Immunocytochemical analyses and targeted gene disruption of GTPBP1. Mol Cell Biol 20:6195–6200CrossRefGoogle Scholar
  34. Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25:302–305. CrossRefPubMedGoogle Scholar
  35. Telonis-Scott M, van Heerwaarden B, Johnson TK, Hoffmann AA, Sgrò CM (2013) New levels of transcriptome complexity at upper thermal limits in wild Drosophila revealed by exon expression analysis. Genetics 195:809–830. CrossRefPubMedPubMedCentralGoogle Scholar
  36. Vienne J, Spann R, Guo F, Rosbash M (2016) Age-related reduction of recovery sleep and arousal threshold in Drosophila. Sleep 39:1613–1624. CrossRefPubMedPubMedCentralGoogle Scholar
  37. Walkinshaw E, Gai Y, Farkas C, Richter D, Nicholas E, Keleman K, Davis RL (2015) Identification of genes that promote or inhibit olfactory memory formation in Drosophila. Genetics 199:1173–1182. CrossRefPubMedPubMedCentralGoogle Scholar
  38. Woo KC, Kim TD, Lee KH, Kim DY, Kim S, Lee HR, Kang HJ, Chung SJ, Senju S, Nishimura Y, Kim KT (2011) Modulation of exosome-mediated mRNA turnover by interaction of GTP-binding protein 1 (GTPBP1) with its target mRNAs. FASEB J 25:2757–2769. CrossRefPubMedGoogle Scholar
  39. Zinoviev A, Goyal A, Jindal S, LaCava J, Komar AA, Rodnina MV, Hellen CUT, Pestova TV (2018) Functions of unconventional mammalian translational GTPases GTPBP1 and GTPBP2. Genes Dev 32:1226–1241. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory of Amyloid BiologySt. Petersburg State UniversitySaint PetersburgRussia
  2. 2.Laboratory of Comparative Behavioral GeneticsPavlov Institute of Physiology of the Russian Academy of SciencesSaint PetersburgRussia

Personalised recommendations