Abstract
Heat shock proteins, in particular Hsp70, play a central role in proteostasis in eukaryotic cells. Due to its chaperone properties, Hsp70 is involved in various processes after stress and under normal physiological conditions. In contrast to mammals and many Diptera species, inducible members of the Hsp70 family in Drosophila are constitutively synthesized at a low level and undergo dramatic induction after temperature elevation or other forms of stress. In the courtship suppression paradigm used in this study, Drosophila males that have been repeatedly rejected by mated females during courtship are less likely than naive males to court other females. Although numerous genes with known function were identified to play important roles in long-term memory, there is, to the best of our knowledge, no direct evidence implicating Hsp70 in this process. To elucidate a possible role of Hsp70 in memory formation, we used D. melanogaster strains containing different hsp70 copy numbers, including strains carrying a deletion of all six hsp70 genes. Our investigations exploring the memory of courtship rejection paradigm demonstrated that a low constitutive level of Hsp70 is apparently required for learning and the formation of short and long-term memories in males. The performed transcriptomic studies demonstrate that males with different hsp70 copy numbers differ significantly in the expression of a few definite groups of genes involved in mating, reproduction, and immunity in response to rejection. Specifically, our analysis reveals several major pathways that depend on the presence of hsp70 in the genome and participate in memory formation and consolidation, including the cAMP signaling cascade.
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Akalal D-BG, Yu D, Davis RL (2010) A late-phase, long-term memory trace forms in the γ neurons of Drosophila mushroom bodies after olfactory classical conditioning. J Neurosci 30:16699–16708. https://doi.org/10.1523/JNEUROSCI.1882-10.2010
Akalal D-BG, Yu D, Davis RL (2011) The long-term memory trace formed in the Drosophila α/β mushroom body neurons is abolished in long-term memory mutants. J Neurosci 31:5643–5647. https://doi.org/10.1523/JNEUROSCI.3190-10.2011
Ambrosini MV, Mariucci G, Tantucci M, Van Hooijdonk L, Ammassari-Teule M (2005) Hippocampal 72-kDa heat shock protein expression varies according to mice learning performance independently from chronic exposure to stress. Hippocampus 15:413–417. https://doi.org/10.1002/hipo.20069
Ammon-Treiber S, Grecksch G, Angelidis C, Vezyraki P, Höllt V, Becker A (2008) Emotional and learning behaviour in mice overexpressing heat shock protein 70. Neurobiol Learn Mem 90:358–364. https://doi.org/10.1016/j.nlm.2008.04.006
Anaka M, Macdonald CD, Barkova E, Simon K, Rostom R, Godoy RA, Haigh AJ, Meinertzhagen IA, Lloyd V (2008) The white gene of Drosophila melanogaster encodes a protein with a role in courtship behavior. J Neurogenet 22:243–276. https://doi.org/10.1080/01677060802309629
Astakhova LN, Zatsepina OG, Funikov SY, Zelentsova ES, Schostak NG, Orishchenko KE, Evgen’ev MB, Garbuz DG (2015) Activity of heat shock genes' promoters in thermally contrasting animal species. PLoS One 10:e0115536. https://doi.org/10.1371/journal.pone.0115536
Bailey CH, Bartsch D, Kandel ER (1996) Toward a molecular definition of long-term memory storage. Proc Natl Acad Sci 93:13445–13452. https://doi.org/10.1073/pnas.93.24.13445
Barajas-Azpeleta R, Wu J, Gill J, Welte R, Seidel C, McKinney S, Dissel S, Si K (2018) Antimicrobial peptides modulate long-term memory. PLoS Genet 14:e1007440. https://doi.org/10.1371/journal.pgen.1007440
Beck CD, Schroeder B, Davis RL (2000) Learning performance of normal and mutant Drosophila after repeated conditioning trials with discrete stimuli. J Neurosci 20:2944–2953. https://doi.org/10.1523/JNEUROSCI.20-08-02944.2000
Billeter JC, Villella A, Allendorfer JB, Dornan AJ, Richardson M, Gailey DA, Goodwin SF (2006) Isoform-specific control of male neuronal differentiation and behavior in Drosophila by the fruitless gene. Curr Biol 16:1063–1076. https://doi.org/10.1016/j.cub.2006.04.039
Bobkova NV, Evgen'ev M, Garbuz DG, Kulikov AM, Morozov A et al (2015) Exogenous Hsp70 delays senescence and improves cognitive function in aging mice. Proc Natl Acad Sci U S A 112:16006–16011. https://doi.org/10.1073/pnas.1516131112
Bobkova NV, Garbuz DG, Nesterova I, Medvinskaya N, Samokhin A, Alexandrova I, Yashin V, Karpov V, Kukharsky MS, Ninkina NN, Smirnov AA, Nudler E, Evgen'ev M (2014) Therapeutic effect of exogenous hsp70 in mouse models of Alzheimer's disease. J Alzheimers Dis 38:425–435. https://doi.org/10.3233/JAD-130779
Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30:2114–2120. https://doi.org/10.1093/bioinformatics/btu170
Bozler J, Kacsoh BZ, Chen H, Theurkauf WE, Weng Z, Bosco G (2017) A systems level approach to temporal expression dynamics in Drosophila reveals clusters of long term memory genes. PLoS Genet 13:e1007054. https://doi.org/10.1371/journal.pgen.1007054
Carman A, Kishinevsky S, Koren J, Lou W, Chiosis G (2013) Chaperone-dependent Neurodegeneration: a molecular perspective on therapeutic intervention. J Alzheimers Dis Parkinsonism 2013:s10. https://doi.org/10.4172/2161-0460.S10-007
Ciechanover A, Kwon YT (2017) Protein quality control by molecular chaperones in neurodegeneration. Front Neurosci 11:185. https://doi.org/10.3389/fnins.2017.00185
Cowan TM, Siegel RW (1986) Drosophila mutations that alter ionic conduction disrupt acquisition and retention of a conditioned odor avoidance response. J Neurogenet 3:187–201. https://doi.org/10.3109/01677068609106849
Dahlgaard J, Loeschcke V, Michalak P, Justesen J (1998) Induced thermotolerance and associated expression of the heat-shock protein Hsp70 in adult Drosophila melanogaster. Funct Ecol 12:786–793
Davis RL (2005) Olfactory memory formation in Drosophila: from molecular to systems neuroscience. Annu Rev Neurosci 28:275–302. https://doi.org/10.1146/annurev.neuro.28.061604.135651
Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29:15–21. https://doi.org/10.1093/bioinformatics/bts635
Donovan MR, Marr MT 2nd (2016) dFOXO activates large and small heat shock protein genes in response to oxidative stress to maintain proteostasis in drosophila. J Biol Chem 291(36):19042–19050. https://doi.org/10.1074/jbc.M116.723049
Dubnau J, Tully T (1998) Gene discovery in Drosophila: new insights for learning and memory. Annu Rev Neurosci 21:407–444. https://doi.org/10.1146/annurev.neuro.21.1.407
Durand N, Pottier MA, Siaussat D, Bozzolan F, Maïbèche M, Chertemps T (2018) Glutathione-S-transferases in the olfactory organ of the noctuid moth. Front Physiol 9:1283. https://doi.org/10.3389/fphys.2018.01283
Evgen'ev M, Levin A, Lozovskaya E (1979) The analysis of a temperature-sensitive (ts) mutation influencing the expression of heat shock-inducible genes in Drosophila melanogaster. Mol Gen Genet 176:275–280. https://doi.org/10.1007/BF00273222
Evgen'ev MB, Garbuz DG, Zatsepina OG (2014) Heat shock proteins and whole body adaptation to extreme environments. Springer, Berlin
Fedotov SA, Besedina NG, Bragina JV, Danilenkova LV, Kamysheva EA, Kamyshev NG (2020) The involvement of neurons expressing gene factor of interpulse interval (fipi) in regulation of courtship behavior of Drosophila melanogaster males. Integr Physiol 4:366–379. https://doi.org/10.33910/2687-1270-2020-1-4-365-378
Fleshner M, Campisi J, Amiri L, Diamond D (2004) Cat exposure induces both intra- and extracellular Hsp72: the role of adrenal hormones. Psychoneuroendocrinology 29:1142–1152. https://doi.org/10.1016/j.psyneuen.2004.01.007
Flexner JB, Flexner LB, Stellar E (1963) Memory in mice as affected by intracerebral puromycin. Science 141:57–59. https://doi.org/10.1126/science.141.3575.57
Foster NL, Lukowiak K, Henry TB (2015) Time-related expression profiles for heat shock protein gene transcripts (HSP40, HSP70) in the central nervous system of Lymnaea stagnalis exposed to thermal stress. Commun Integr Biol 8:e1040954. https://doi.org/10.1080/19420889.2015.1040954
Fukudo S, Abe K, Hongo M, Utsumi A, Itoyama Y (1997) Brain-gut induction of heat shock protein (HSP) 70 mRNA by psychophysiological stress in rats. Brain Res 757(1):146–148. https://doi.org/10.1016/s0006-8993(97)00179-0
Fukudo S, Abe K, Itoyama Y, Mochizuki S, Sawai T, Hongo M (1999) Psychophysiological stress induces heat shock cognate protein 70 messenger RNA in the hippocampus of rats. Neuroscience. 91(4):1205–1208. https://doi.org/10.1016/s0306-4522(99)00069-x
Ge X, Hannan F, Xie Z, Feng C, Tully T, Zhou H, Xie Z, Zhong Y (2004) Notch signaling in Drosophila long-term memory formation. Proc Natl Acad Sci U S A 101:10172–10176. https://doi.org/10.1073/pnas.0403497101
Gerstner JR, Yin JC (2010) Circadian rhythms and memory formation. Nat Rev Neurosci 11:577–588. https://doi.org/10.1038/nrn2881
Godenschwege TA, Reisch D, Diegelmann S, Eberle K, Funk N, Heisenberg M, Hoppe V, Hoppe J, Klagges BRE, Martin JR, Nikitina EA, Putz G, Reifegerste R, Reisch N, Rister J, Schaupp M, Scholz H, Schwarzel M, Werner U, Zars TD, Buchner S, Buchner E (2004) Flies lacking all synapsins are unexpectedly healthy but are impaired in complex behaviour. Eur J Neurosci 20(3):611–622. https://doi.org/10.1111/j.1460-9568.2004.03527.x
Gong WJ, Golic KG (2004) Genomic deletions of the Drosophila melanogaster Hsp70 genes. Genetics 168:1467–1476. https://doi.org/10.1534/genetics.104.030874
Gonzalez D, Fraichard S, Grassein P, Delarue P, Senet P, Nicolaï A, Chavanne E, Mucher E, Artur Y, Ferveur JF, Heydel JM, Briand L, Neiers F (2018) Characterization of a Drosophila glutathione transferase involved in isothiocyanate detoxification. Insect Biochem Mol Biol 95:33–43. https://doi.org/10.1016/j.ibmb.2018.03.004
Griffith LC, Ejima A (2009) Courtship learning in Drosophila melanogaster: diverse plasticity of a reproductive behavior. Learn Mem 16:743–750. https://doi.org/10.1101/lm.956309
Guan Z, Buhl LK, Quinn WG, Littleton JT (2011) Altered gene regulation and synaptic morphology in Drosophila learning and memory mutants. Learn Mem 18:191–206. https://doi.org/10.1101/lm.2027111
Gupta S, Kim SY, Artis S, Molfese DL, Schumacher A, Sweatt JD, Paylor RE, Lubin FD (2010) Histone methylation regulates memory formation. J Neurosci 30:3589–3599. https://doi.org/10.1523/JNEUROSCI.3732-09.2010
Gyurko DM, Soti C, Stetak A, Csermely P (2014) System level mechanisms of adaptation, learning, memory formation and evolvability: the role of chaperone and other networks. Curr Protein Pept Sci 15:171–188. https://doi.org/10.2174/1389203715666140331110522
Harris N, Braiser DJ, Dickman DK, Fetter RD, Tong A, Davis GW (2015) The innate immune receptor PGRP-LC controls presynaptic homeostatic plasticity. Neuron 88:1157–1164. https://doi.org/10.1016/j.neuron.2015.10.049
Hartl FU, Bracher A, Hayer-Hartl M (2011) Molecular chaperones in protein folding and proteostasis. Nature 475:324–332. https://doi.org/10.1038/nature10317
Hooper PL, Durham HD, Török Z, Crul T, Vígh L (2016) The central role of heat shock factor 1 in synaptic fidelity and memory consolidation. Cell Stress Chaperones 21:745–753. https://doi.org/10.1007/s12192-016-0709-1
Igaz LM, Bekinschtein P, Izquierdo I, Medina JH (2004) One-trial aversive learning induces late changes in hippocampal CaMKIIα, Homer 1a, Syntaxin 1a and ERK2 protein levels. Mol Brain Res 132:1–12. https://doi.org/10.1016/j.molbrainres.2004.08.016
Ishimoto H, Sakai T, Kitamoto T (2009) Ecdysone signaling regulates the formation of long-term courtship memory in adult Drosophila melanogaster. Proc Natl Acad Sci U S A 106:6381–6386. https://doi.org/10.1073/pnas.0810213106
Jones SG, Nixon KC, Chubak MC, Kramer JM (2018) Mushroom body specific transcriptome analysis reveals dynamic regulation of learning and memory genes after acquisition of long-term courtship memory in Drosophila. G3: Genes. Genom Genet 8:3433–3446. https://doi.org/10.1534/g3.118.200560
Kabil H, Kabil O, Banerjee R, Harshman LG, Pletcher SD (2011) Increased transsulfuration mediates longevity and dietary restriction in Drosophila. Proc Natl Acad Sci U S A 108:16831–16836. https://doi.org/10.1073/pnas.1102008108
Kagawa N, Ryo K, Mugiya Y (1999) Enhanced expression of stress protein 70 in the brains of goldfish, Carassius auratus, reared with bluegills, Lepomis macrochirus. Fish Physiol Biochem 21:103–110. https://doi.org/10.2108/zsj.17.1061
Kahsai L, Zars T (2011) Learning and memory in Drosophila: behavior, genetics, and neural systems. Int Rev Neurobiol 99:139–167. https://doi.org/10.1016/B978-0-12-387003-2.00006-9
Kaletsky R, Lakhina V, Arey R, Williams A, Landis J, Ashraf J, Murphy CT (2016) The C. elegans adult neuronal IIS/FOXO transcriptome reveals adult phenotype regulators. Nature 529(7584):92–96. https://doi.org/10.1038/nature16483
Kamyshev NG, Iliadi KG, Bragina JV (1999) Drosophila conditioned courtship: two ways of testing memory. Learn Mem 6:1–20
Kandel ER (2001) The molecular biology of memory storage: a dialogue between genes and synapses. Science 294:1030–1038. https://doi.org/10.1126/science.1067020
Kandel ER (2012) The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB. Mol Brain 5:14. https://doi.org/10.1186/1756-6606-5-14
Keleman K, Krüttner S, Alenius M, Dickson BJ (2007) Function of the Drosophila CPEB protein Orb2 in long-term courtship memory. Nat Neurosci 10:1587–1593. https://doi.org/10.1038/nn1996
Kennedy D, Jäger R, Mosser DD, Samali A (2014) Regulation of apoptosis by heat shock proteins. IUBMB Life 66:327–338. https://doi.org/10.1002/iub.1274
Kim JY, Yenari MA (2013) The immune modulating properties of the heat shock proteins after brain injury. Anatol Cell Biol 46:1–7. https://doi.org/10.5115/acb.2013.46.1.1
Kim SY, Webb AE (2017) Neuronal functions of FOXO/DAF-16. Nutr Healthy Aging 4(2):113–126. https://doi.org/10.3233/NHA-160009
Kimura H (2014) Production and physiological effects of hydrogen sulfide. Antioxid Redox Signal 20:783–793. https://doi.org/10.1089/ars.2013.5309
Krasnov GS, Dmitriev AA, Kudryavtseva AV, Shargunov AV, Karpov DS, Uroshlev LA, Melnikova NV, Blinov VM, Poverennaya EV, Archakov AI, Lisitsa AV, Ponomarenko EA (2015) PPLine: An automated pipeline for SNP, SAP, and splice variant detection in the context of proteogenomics. J Proteome Res 14:3729–3737. https://doi.org/10.1021/acs.jproteome.5b00490
Kumar A, Tiwari AK (2018) Molecular chaperone Hsp70 and its constitutively active form Hsc70 play an indispensable role during eye development of Drosophila melanogaster. Mol Neurobiol 55:4345–4361. https://doi.org/10.1007/s12035-017-0650-z
Kuntz S, Poeck B, Strauss R (2017) Visual working memory requires permissive and instructive NO/cGMP signaling at presynapses in the Drosophila central brain. Curr Biol 27:613–623. https://doi.org/10.1016/j.cub.2016.12.056
Kuzin BA, Nikitina EA, Cherezov RO, Vorontsova JE, Slezinger MS, Zatsepina OG, Simonova OB, Enikolopov GN, Savvateeva-Popova EV (2014) Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification. PLoS One 9:e94975. https://doi.org/10.1371/journal.pone.0094975
Kwon HJ, Kim W, Jung HY, Kang MS, Kim JW, Hahn KR, Yoo DY, Yoon YS, Hwang IK, Kim DW (2019) Heat shock protein 70 increases cell proliferation, neuroblast differentiation, and the phosphorylation of CREB in the hippocampus. Lab Anim Res 35:21. https://doi.org/10.1186/s42826-019-0020-2
Levin LR, Han PL, Hwang PM, Feinstein PG, Davis RL, Reed RR (1992) The Drosophila learning and memory gene rutabaga encodes a Ca2+/Calmodulin-responsive adenylyl cyclase. Cell 68:479–489. https://doi.org/10.1016/0092-8674(92)90185-f
Livingstone MS, Sziber PP, Quinn WG (1984) Loss of calcium/calmodulin responsiveness in adenylate cyclase of rutabaga, a Drosophila learning mutant. Cell 37:205–215. https://doi.org/10.1016/0092-8674(84)90316-7
Lukowiak K, Orr M, de Caigny P, Lukowiak KS, Rosenegger D, Han JI, Dalesman S (2010) Ecologically relevant stressors modify long-term memory formation in a model system. Behav Brain Res 214:18–24. https://doi.org/10.1016/j.bbr.2010.05.011
Martín-Peña A, Rincón-Limas DE, Fernandez-Fúnez P (2018) Engineered Hsp70 chaperones prevent Aβ42-induced memory impairments in a Drosophila model of Alzheimer’s disease. Sci Rep 8:1–14. https://doi.org/10.1038/s41598-018-28341-w
Mastushita-Sakai T, White-Grindley E, Samuelson J, Seidel C, Si K (2010) Drosophila Orb2 targets genes involved in neuronal growth, synapse formation, and protein turnover. Proc Natl Acad Sci U S A 107:11987–11992. https://doi.org/10.1073/pnas.1004433107
McBride SM, Giuliani G, Choi C, Krause P, Correale D et al (1999) Mushroom body ablation impairs short-term memory and long-term memory of courtship conditioning in Drosophila melanogaster. Neuron 24:967–977. https://doi.org/10.1016/s0896-6273(00)81043-0
McDonald MJ, Rosbash M (2001) Microarray analysis and organization of circadian gene expression in Drosophila. Cell 107:567–578. https://doi.org/10.1016/s0092-8674(01)00545-1
Mery F, Belay AT, So AK-C, Sokolowski MB, Kawecki TJ (2007) Natural polymorphism affecting learning and memory in Drosophila. Proc Natl Acad Sci 104:13051–13055. https://doi.org/10.1073/pnas.0702923104
Murshid A, Chou SD, Prince T, Zhang Y, Bharti A, Calderwood SK (2010) Protein kinase A binds and activates heat shock factor 1. PLoS One 5:e13830. https://doi.org/10.1371/journal.pone.0013830
Nagai Y, Tsugane M, Oka J, Kimura H (2004) Hydrogen sulfide induces calcium waves in astrocytes. FASEB J 18:557–559. https://doi.org/10.1096/fj.03-1052fje
Nagpure BV, Bian JS (2015) Brain, learning, and memory: role of H2S in neurodegenerative diseases. Handb Exp Pharmacol 230:193–215. https://doi.org/10.1007/978-3-319-18144-8_10
Nikitina E, Tokmatcheva E, Savateeva-Popova E (2003) Heat shock during the development of central structures of the Drosophila brain: memory formation in the l (1) ts403 mutant of Drosophila melanogaster. Russ J Genet 39:25–31
Obata F, Kuranaga E, Tomioka K, Ming M, Takeishi A, Chen CH, Soga T, Miura M (2014) Necrosis-driven systemic immune response alters SAM metabolism through the FOXO-GNMT axis. Cell Rep 7:821–833. https://doi.org/10.1016/j.celrep.2014.03.046
Obata F, Miura M (2015) Enhancing S-adenosyl-methionine catabolism extends Drosophila lifespan. Nat Commun 6:8332. https://doi.org/10.1038/ncomms9332
Orr WC, Radyuk SN, Prabhudesai L, Toroser D, Benes JJ, Luchak JM, Mockett RJ, Rebrin I, Hubbard JG, Sohal RS (2005) Overexpression of glutamate-cysteine ligase extends life span in Drosophila melanogaster. J Biol Chem 280:37331–37338. https://doi.org/10.1074/jbc.M508272200
Paul BD, Snyder SH (2015) H2S: A novel gasotransmitter that signals by sulfhydration. Trends Biochem Sci 40:687–700. https://doi.org/10.1016/j.tibs.2015.08.007
Peixoto L, Abel T (2013) The role of histone acetylation in memory formation and cognitive impairments. Neuropsychopharmacology 38:62–76. https://doi.org/10.1038/npp.2012.86
Pijanowska J, Kloc M (2004) Daphnia response to predation threat involves heat-shock proteins and the actin and tubulin cytoskeleton. Genesis. 38(2):81–86. https://doi.org/10.1002/gene.20000
Pizarro JM, Haro LS, Barea-Rodriguez EJ (2003) Learning associated increase in heat shock cognate 70 mRNA and protein expression. Neurobiol Learn Mem 79:142–151. https://doi.org/10.1016/s1074-7427(02)00008-4
Ponton F, Chapuis MP, Pernice M, Sword GA, Simpson SJ (2011) Evaluation of potential reference genes for reverse transcription-qPCR studies of physiological responses in Drosophila melanogaster. J Insect Physiol 57:840–850. https://doi.org/10.1016/j.jinsphys.2011.03.014
Porto RR, Dutra FD, Crestani AP, Holsinger RMD, Quillfeldt JA, Homem de Bittencourt PI Jr, de Oliveira Alvares L (2018) HSP70 Facilitates memory consolidation of fear conditioning through MAPK pathway in the hippocampus. Neuroscience 375:108–118. https://doi.org/10.1016/j.neuroscience.2018.01.028
Presente A, Boyles RS, Serway CN, de Belle JS, Andres AJ (2004) Notch is required for long-term memory in Drosophila. Proc Natl Acad Sci U S A 101:1764–1768. https://doi.org/10.1073/pnas.0308259100
Redt-Clouet C, Trannoy S, Boulanger A, Tokmatcheva E, Savvateeva-Popova E, Parmentier ML, Preat T, Dura JM (2012) Mushroom body neuronal remodelling is necessary for short-term but not for long-term courtship memory in Drosophila. Eur J Neurosci 35(11):1684–1691. https://doi.org/10.1111/j.1460-9568.2012.08103.x
Renger JJ, Ueda A, Atwood HL, Govind CK, Wu CF (2000) Role of cAMP cascade in synaptic stability and plasticity: ultrastructural and physiological analyses of individual synaptic boutons in Drosophila memory mutants. J Neurosci 20:3980–3992. https://doi.org/10.1523/JNEUROSCI.20-11-03980.2000
Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26:139–140. https://doi.org/10.1093/bioinformatics/btp616
Rohlf FJ, Sokal RR (1981) Biometry: the principles and practice of statistics in biological research. Freeman New York
Sakai T, Kitamoto T (2006) Clock, love and memory: circadian and non-circadian regulation of Drosophila mating behavior by clock genes. Sleep Biol Rhythms 4:255–262
Santana E, de Los RT, Casas-Tintó S (2020) Small heat shock proteins determine synapse number and neuronal activity during development. PLoS One 15(5):e0233231. https://doi.org/10.1371/journal.pone.0233231
Savvateeva EV, Popov AV, Kamyshev NG, Iliadi KG, Bragina JV, Heisenberg M, Kornhuber J, Riederer P (1999) Age-dependent changes in memory and mushroom bodies in the Drosophila mutant vermilion deficient in the kynurenine pathway of tryptophan metabolism. Ross Fiziol Zh Im I M Sechenova 85:167–183
Savvateeva E, Popov A, Kamyshev N, Bragina J, Heisenberg M, Senitz D, Kornhuber J, Riederer P (2000) Age-dependent memory loss, synaptic pathology and altered brain plasticity in the Drosophila mutant cardinal accumulating 3-hydroxykynurenine. J Neural Transm (Vienna) 107(5):581–601. https://doi.org/10.1007/s007020070080
Savvateeva-Popova E, Popov A, Grossman A, Nikitina E, Medvedeva A, Molotkov D, Kamyshev N, Pyatkov K, Zatsepina O, Schostak N, Zelentsova E, Pavlova G, Panteleev D, Riederer P, Evgen`ev M (2008) Non-coding RNA as a trigger of neuropathologic disorder phenotypes in transgenic Drosophila. J Neural Transm (Vienna) 115:1629–1642. https://doi.org/10.1007/s00702-008-0078-8
Savvateeva-Popova E, Popov A, Grossman A, Nikitina E, Medvedeva A, Peresleni A, Korochkin L, Moe JG, Davidowitz E, Pyatkov K, Myasnyankina E, Zatsepina O, Schostak N, Zelentsova E, Evgen'ev M (2007) Pathogenic chaperone-like RNA induces congophilic aggregates and facilitates neurodegeneration in Drosophila. Cell Stress Chaperones 12:9–19. https://doi.org/10.1379/csc-222r.1
Savvateeva-Popova EV, Zhuravlev AV, Brázda V, Zakharov GA, Kaminskaya AN, Medvedeva AV, Nikitina EA, Tokmatcheva EV, Dolgaya JF, Kulikova DA, Zatsepina OG, Funikov SY, Ryazansky SS, Evgen‘ev MB (2017) Model for the analysis of genesis of LIM-kinase 1-dependent Williams-Beuren syndrome cognitive phenotypes: INDELs, transposable elements of the Tc1/. Front Genet 8:123. https://doi.org/10.3389/fgene.2017.00123
Scaccianoce S, Del Bianco P, Caricasole A, Nicoletti F, Catalani A (2003) Relationship between learning, stress and hippocampal brain-derived neurotrophic factor. Neuroscience 121:825–828. https://doi.org/10.1016/s0306-4522(03)00514-1
Schefe JH, Lehmann KE, Buschmann IR, Unger T, Funke-Kaiser H (2006) Quantitative real-time RT-PCR data analysis: current concepts and the novel "gene expression's CT difference" formula. J Mol Med (Berl) 84:901–910. https://doi.org/10.1007/s00109-006-0097-6
Shilova VY, Zatsepina OG, Garbuz DG, Funikov SY, Zelentsova ES, Schostak NG, Kulikov AM, Evgen'ev MB (2018) Heat shock protein 70 from a thermotolerant Diptera species provides higher thermoresistance to Drosophila larvae than correspondent endogenous gene. Insect Mol Biol 27:61–72. https://doi.org/10.1111/imb.12339
Sitaraman D, Zars M, Laferriere H, Chen YC, Sable-Smith A et al (2008) Serotonin is necessary for place memory in Drosophila. Proc Natl Acad Sci U S A 105:5579–5584. https://doi.org/10.1073/pnas.0710168105
Snijder PM, Baratashvili M, Grzeschik NA, Leuvenink HGD, Kuijpers L, Huitema S, Schaap O, Giepmans BNG, Kuipers J, Miljkovic JL, Mitrovic A, Bos EM, Szabó C, Kampinga HH, Dijkers PF, Bos EM, Szabó C, Kampinga HH, Dijkers PF, Dunnen WFAD, Filipovic MR, Goor HV, Sibon OCM (2016) Overexpression of Cystathionine γ-lyase suppresses detrimental effects of spinocerebellar ataxia type 3. Mol Med 21:758–768. https://doi.org/10.2119/molmed.2015.00221
Sokolowski MB (2001) Drosophila: genetics meets behaviour. Nat Rev Genet 2:879–890. https://doi.org/10.1038/35098592
Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N, Micheva KD, Mehalow AK, Huberman AD, Stafford B, Sher A, Litke AM, Lambris JD, Smith SJ, John SWM, Barres BA (2007) The classical complement cascade mediates CNS synapse elimination. Cell 131:1164–1178. https://doi.org/10.1016/j.cell.2007.10.036
Sun Y, MacRae TH (2005) Small heat shock proteins: molecular structure and chaperone function. Cell Mol Life Sci 62(21):2460–2476. https://doi.org/10.1007/s00018-005-5190-4
Sunada H, Riaz H, de Freitas E, Lukowiak K, Swinton C, Swinton E, Protheroe A, Shymansky T, Komatsuzaki Y, Lukowiak K (2016) Heat stress enhances LTM formation in Lymnaea: role of HSPs and DNA methylation. J Exp Biol 219:1337–1345. https://doi.org/10.1242/jeb.134296
Suzuki T, Usuda N, Murata S, Nakazawa A, Ohtsuka K, Takagi H (1999) Presence of molecular chaperones, heat shock cognate (Hsc) 70 and heat shock proteins (Hsp) 40, in the postsynaptic structures of rat brain. Brain Res 816:99–110. https://doi.org/10.1016/s0006-8993(98)01083-x
Thekkuveettil A, Lakhotia SC (1996) Regulation of HSP70 in excitatory neurons: Possible implications for neuronal functioning. J Biosci 21:631–639. https://doi.org/10.1007/BF02703141
Timpe LC, Schwarz TL, Tempel BL, Papazian DM, Jan YN, Jan LY (1988) Expression of functional potassium channels from Shaker cDNA in Xenopus oocytes. Nature 331:143–145. https://doi.org/10.1038/331143a0
Tully T (1996) Discovery of genes involved with learning and memory: an experimental synthesis of Hirschian and Benzerian perspectives. Proc Natl Acad Sci 93:13460–13467
Tully T, Boynton S, Brandes C, Dura JM, Mihalek R, Preat T, Villella A (1990) Genetic dissection of memory formation in Drosophila melanogaster. Cold Spring Harb Symp Quant Biol 55:203–211. https://doi.org/10.1101/sqb.1990.055.01.022
Tully T, Preat T, Boynton SC, Del Vecchio M (1994) Genetic dissection of consolidated memory in Drosophila. Cell 79:35–47. https://doi.org/10.1016/0092-8674(94)90398-0
Winbush A, Reed D, Chang PL, Nuzhdin SV, Lyons LC, Arbeitman MN (2012) Identification of gene expression changes associated with long-term memory of courtship rejection in Drosophila males. G3: Genes, Genomes, Genetics 2:1437–1445. https://doi.org/10.1534/g3.112.004119
Witt SN (2013) Molecular chaperones, α-synuclein, and neurodegeneration. Mol Neurobiol 47:552–560. https://doi.org/10.1007/s12035-012-8325-2
Wyatt AR, Yerbury JJ, Ecroyd H, Wilson MR (2013) Extracellular chaperones and proteostasis. Annu Rev Biochem 82:295–322. https://doi.org/10.1146/annurev-biochem-072711-163904
Xu S, Wilf R, Menon T, Panikker P, Sarthi J, Elefant F (2014) Epigenetic control of learning and memory in Drosophila by Tip60 HAT action. Genetics 198:1571–1586. https://doi.org/10.1534/genetics.114.171660
Yao WD, Wu CF (2001) Distinct roles of CaMKII and PKA in regulation of firing patterns and K(+) currents in Drosophila neurons. J Neurophysiol 85(4):1384–1394. https://doi.org/10.1152/jn.2001.85.4.1384
Yong QC, Choo CH, Tan BH, Low CM, Bian JS (2010) Effect of hydrogen sulfide on intracellular calcium homeostasis in neuronal cells. Neurochem Int 56:508–515. https://doi.org/10.1016/j.neuint.2009.12.011
Yu D, Akalal D-BG, Davis RL (2006) Drosophila α/β mushroom body neurons form a branch-specific, long-term cellular memory trace after spaced olfactory conditioning. Neuron 52:845–855. https://doi.org/10.1016/j.neuron.2006.10.030
Yu G, Wang LG, Han Y, He QY (2012) clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16:284–287. https://doi.org/10.1089/omi.2011.0118
Yurinskaya MM, Krasnov GS, Kulikova DA, Zatsepina OG, Vinokurov MG, Chuvakova LN, Rezvykh AP, Funikov SY, Morozov AV, Evgen’ev MB (2020) H2S counteracts proinflammatory effects of LPS through modulation of multiple pathways in human cells. Inflamm Res 69:481–495. https://doi.org/10.1007/s00011-020-01329-x
Zars T (2017) Working memory: It’sa gas, gas, gas. Curr Biol 27:R179–RR81. https://doi.org/10.1016/j.cub.2017.01.005
Zhang J, Little CJ, Tremmel DM, Yin JC, Wesley CS (2013) Notch-inducible hyperphosphorylated CREB and its ultradian oscillation in long-term memory formation. J Neurosci 33:12825–12834. https://doi.org/10.1523/JNEUROSCI.0783-13.2013
Zhao Z, Sabirzhanov B, Wu J, Faden AI, Stoica BA (2015) Voluntary exercise preconditioning activates multiple antiapoptotic mechanisms and improves neurological recovery after experimental traumatic brain injury. J Neurotrauma 32:1347–1360. https://doi.org/10.1089/neu.2014.3739
Zhong Y, Wu CF (1993) Differential modulation of potassium currents by cAMP and its long-term and short-term effects: dunce and rutabaga mutants of Drosophila. J Neurogenet 9:15–27. https://doi.org/10.3109/01677069309167273
Zhou C, Huang H, Kim SM, Lin H, Meng X, Han KA, Chiang AS, Wang JW, Jiao R, Rao Y (2012) Molecular genetic analysis of sexual rejection: roles of octopamine and its receptor OAMB in Drosophila courtship conditioning. J Neurosci 32:14281–14287. https://doi.org/10.1523/JNEUROSCI.0517-12.2012
Zhuravlev A, Nikitina E, Savvateeva-Popova E (2015) Learning and memory in Drosophila: physiologic and genetic bases. Usp Fiziol Nauk 46:76–92
Zovkic IB, Guzman-Karlsson MC, Sweatt JD (2013) Epigenetic regulation of memory formation and maintenance. Learn Mem 20:61–74. https://doi.org/10.1101/lm.026575.112
Acknowledgements
The bioinformatics was performed using the computational facilities of Engelhardt Institute of Molecular Biology RAS Genome center (http://www.eimb.ru/rus/ckp/ccu_genome_c.php).
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Sequence data were deposited in the NCBI GEO database under the number GSE152647.
Funding
All genetic and behavioral experiments were supported by the Russian Foundation for Basic Research grant no. 18-04-00865 (to O.Z.). Transcriptomic studies were funded by Russian Science Foundation Grant 17-74-30030 to M.E.
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Study conception and design were performed by (Evgen’ev M.B., Zatsepina O.G., Nikitina E.A.). Material preparation, data collection, and analysis were performed by (Shilova V.Y., Chuvakova L.N., Sorokina S., Tokmacheva E.V.). Libraries for RNA-seq were prepared by (Chuvakova L.N., Funikov S.Y.). Differential gene expression analysis was performed by (Rezvykh A.P.). Construction of Elav GFP/FM7; Hsp70-/Hsp70- strain for confocal analysis was done by Vorontsova J.E. The first draft of the manuscript was written by (Zatsepina O.G., Nikitina E.A., Evgen’ev M.B.). All authors read and approved the final manuscript.
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Zatsepina, O.G., Nikitina, E.A., Shilova, V.Y. et al. Hsp70 affects memory formation and behaviorally relevant gene expression in Drosophila melanogaster. Cell Stress and Chaperones 26, 575–594 (2021). https://doi.org/10.1007/s12192-021-01203-7
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DOI: https://doi.org/10.1007/s12192-021-01203-7