Overexpression of isoform B of Dgp-1 gene enhances locomotor activity in senescent Drosophila males and under heat stress
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.
KeywordsLocomotion Heat stress Senescence Oxidative stress Drosophila Dgp-1 mutant
Age-related locomotor impairments
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.
For this type of study, formal consent is not required.
- 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
- 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. https://doi.org/10.1371/journal.pbio.2001655 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1371/journal.pone.0037250 CrossRefPubMedPubMedCentralGoogle Scholar
- Edgington ES (1995) Randomization tests. Marcel Dekker, New YorkGoogle Scholar
- 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. https://doi.org/10.4161/19336934.2014.983389 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1016/j.freeradbiomed.2009.03.025 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1371/journal.pone.0130334 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1371/journal.pgen.1000814 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1016/j.exger.2008.04.011 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1534/genetics.113.156224 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1096/fj.10-178715 CrossRefPubMedGoogle Scholar