Proteomic Mapping of Drosophila Transgenic Elav.L-GAL4/+ Brain As a Tool to Illuminate Neuropathology Mechanisms

Overview

Journal Sci Rep

Specialty Science

Date 2020 Mar 28

PMID 32214222

Authors

Athanassios D Velentzas

Stamatia A Katarachia

Niki E Sagioglou

Maria M Tsioka

Athanasios K Anagnostopoulos

Vassiliki E Mpakou

Eleni I Theotoki

Aikaterini F Giannopoulou

Konstantinos E Keramaris

Issidora S Papassideri

George Th Tsangaris

Dimitrios J Stravopodis

Affiliations

Soon will be listed here.

Abstract

Drosophila brain has emerged as a powerful model system for the investigation of genes being related to neurological pathologies. To map the proteomic landscape of fly brain, in a high-resolution scale, we herein employed a nano liquid chromatography-tandem mass spectrometry technology, and high-content catalogues of 7,663 unique peptides and 2,335 single proteins were generated. Protein-data processing, through UniProt, DAVID, KEGG and PANTHER bioinformatics subroutines, led to fly brain-protein classification, according to sub-cellular topology, molecular function, implication in signaling and contribution to neuronal diseases. Given the importance of Ubiquitin Proteasome System (UPS) in neuropathologies and by using the almost completely reassembled UPS, we genetically targeted genes encoding components of the ubiquitination-dependent protein-degradation machinery. This analysis showed that driving RNAi toward proteasome components and regulators, using the GAL4-elav.L driver, resulted in changes to longevity and climbing-activity patterns during aging. Our proteomic map is expected to advance the existing knowledge regarding brain biology in animal species of major translational-research value and economical interest.

References

Bier E . Drosophila, the golden bug, emerges as a tool for human genetics. Nat Rev Genet. 2005; 6(1):9-23. DOI: 10.1038/nrg1503. View

Bonini N, Fortini M . Human neurodegenerative disease modeling using Drosophila. Annu Rev Neurosci. 2003; 26:627-56. DOI: 10.1146/annurev.neuro.26.041002.131425. View

Jaiswal M, Sandoval H, Zhang K, Bayat V, Bellen H . Probing mechanisms that underlie human neurodegenerative diseases in Drosophila. Annu Rev Genet. 2012; 46:371-96. PMC: 3663445. DOI: 10.1146/annurev-genet-110711-155456. View

Oortveld M, Keerthikumar S, Oti M, Nijhof B, Fernandes A, Kochinke K . Human intellectual disability genes form conserved functional modules in Drosophila. PLoS Genet. 2013; 9(10):e1003911. PMC: 3814316. DOI: 10.1371/journal.pgen.1003911. View

Pandey U, Nichols C . Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery. Pharmacol Rev. 2011; 63(2):411-36. PMC: 3082451. DOI: 10.1124/pr.110.003293. View

Rubin G, Yandell M, Wortman J, Gabor Miklos G, NELSON C, Hariharan I . Comparative genomics of the eukaryotes. Science. 2000; 287(5461):2204-15. PMC: 2754258. DOI: 10.1126/science.287.5461.2204. View

Reiter L, Potocki L, Chien S, Gribskov M, Bier E . A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Res. 2001; 11(6):1114-25. PMC: 311089. DOI: 10.1101/gr.169101. View

Azevedo F, Carvalho L, Grinberg L, Farfel J, Ferretti R, Leite R . Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J Comp Neurol. 2009; 513(5):532-41. DOI: 10.1002/cne.21974. View

Jenett A, Rubin G, Ngo T, Shepherd D, Murphy C, Dionne H . A GAL4-driver line resource for Drosophila neurobiology. Cell Rep. 2012; 2(4):991-1001. PMC: 3515021. DOI: 10.1016/j.celrep.2012.09.011. View

10.

Taniguchi H, Moore A . Chromatin regulators in neurodevelopment and disease: Analysis of fly neural circuits provides insights: Networks of chromatin regulators and transcription factors underlie Drosophila neurogenesis and cognitive defects in intellectual disability and.... Bioessays. 2014; 36(9):872-83. DOI: 10.1002/bies.201400087. View

11.

OKane C . Drosophila as a model organism for the study of neuropsychiatric disorders. Curr Top Behav Neurosci. 2011; 7:37-60. DOI: 10.1007/7854_2010_110. View

12.

Venken K, Simpson J, Bellen H . Genetic manipulation of genes and cells in the nervous system of the fruit fly. Neuron. 2011; 72(2):202-30. PMC: 3232021. DOI: 10.1016/j.neuron.2011.09.021. View

13.

Pfeiffer B, Jenett A, Hammonds A, Ngo T, Misra S, Murphy C . Tools for neuroanatomy and neurogenetics in Drosophila. Proc Natl Acad Sci U S A. 2008; 105(28):9715-20. PMC: 2447866. DOI: 10.1073/pnas.0803697105. View

14.

Zheng Z, Lauritzen J, Perlman E, Robinson C, Nichols M, Milkie D . A Complete Electron Microscopy Volume of the Brain of Adult Drosophila melanogaster. Cell. 2018; 174(3):730-743.e22. PMC: 6063995. DOI: 10.1016/j.cell.2018.06.019. View

15.

Engel J, Wu C . Neurogenetic approaches to habituation and dishabituation in Drosophila. Neurobiol Learn Mem. 2008; 92(2):166-75. PMC: 2730516. DOI: 10.1016/j.nlm.2008.08.003. View

16.

Ramirez J, Martinez A, Lectez B, Lee S, Franco M, Barrio R . Proteomic Analysis of the Ubiquitin Landscape in the Drosophila Embryonic Nervous System and the Adult Photoreceptor Cells. PLoS One. 2015; 10(10):e0139083. PMC: 4604154. DOI: 10.1371/journal.pone.0139083. View

17.

Ding M, Shen K . The role of the ubiquitin proteasome system in synapse remodeling and neurodegenerative diseases. Bioessays. 2008; 30(11-12):1075-83. PMC: 3095215. DOI: 10.1002/bies.20843. View

18.

Patrick G . Synapse formation and plasticity: recent insights from the perspective of the ubiquitin proteasome system. Curr Opin Neurobiol. 2006; 16(1):90-4. DOI: 10.1016/j.conb.2006.01.007. View

19.

Zheng Q, Huang T, Zhang L, Zhou Y, Luo H, Xu H . Dysregulation of Ubiquitin-Proteasome System in Neurodegenerative Diseases. Front Aging Neurosci. 2016; 8:303. PMC: 5156861. DOI: 10.3389/fnagi.2016.00303. View

20.

Giasson B, Lee V . Are ubiquitination pathways central to Parkinson's disease?. Cell. 2003; 114(1):1-8. DOI: 10.1016/s0092-8674(03)00509-9. View