Deletion of endogenous Tau proteins is not detrimental in Drosophila

Sylvie Burnouf, Sebastian Grönke, Hrvoje Augustin, Jacqueline Dols, Marianna Karina Gorsky, Jennifer Werner, Fiona Kerr, Nazif Alic, Pedro Martinez, Linda Partridge

Research output: Contribution to journalArticle

Abstract

Human Tau (hTau) is a highly soluble and natively unfolded protein that binds to microtubules within neurons. Its dysfunction and aggregation into insoluble paired helical filaments is involved in the pathogenesis of Alzheimer’s disease (AD), constituting, together with accumulated ß-amyloid (Aß) peptides, a hallmark of the disease. Deciphering both the loss-of-function and toxic gain-of-function of hTau proteins is crucial to further understand the mechanisms leading to neurodegeneration in AD. As the fruit fly Drosophila melanogaster expresses Tau proteins (dTau) that are homologous to hTau, we aimed to better comprehend dTau functions by generating a specific tau knock-out (KO) fly line using homologous recombination. We observed that the specific removal of endogenous dTau proteins did not lead to overt, macroscopic phenotypes in flies. Indeed, survival, climbing ability and neuronal function were unchanged in tau KO flies. In addition, we did not find any overt positive or negative effect of dTau removal on human Aß-induced toxicity. Altogether, our results indicate that the absence of dTau proteins has no major functional impact on flies, and suggests that our tau KO strain is a relevant model to further investigate the role of dTau proteins in vivo, thereby giving additional insights into hTau functions.
Original languageEnglish
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 15 Mar 2016

Fingerprint

tau Proteins
Diptera
Drosophila
Alzheimer Disease
Intrinsically Disordered Proteins
Proteins
Aptitude
Poisons
Homologous Recombination
Drosophila melanogaster
Amyloid
Microtubules
Fruit
Phenotype
Neurons
Peptides
Survival

Keywords

  • hTau
  • Alzheimer's disease
  • Tau proteins
  • Drosophila
  • neurodegenerative diseases

Cite this

Burnouf, S., Grönke, S., Augustin, H., Dols, J., Gorsky, M. K., Werner, J., ... Partridge, L. (2016). Deletion of endogenous Tau proteins is not detrimental in Drosophila. Scientific Reports, 6. https://doi.org/10.1038/srep23102
Burnouf, Sylvie ; Grönke, Sebastian ; Augustin, Hrvoje ; Dols, Jacqueline ; Gorsky, Marianna Karina ; Werner, Jennifer ; Kerr, Fiona ; Alic, Nazif ; Martinez, Pedro ; Partridge, Linda. / Deletion of endogenous Tau proteins is not detrimental in Drosophila. In: Scientific Reports. 2016 ; Vol. 6.
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abstract = "Human Tau (hTau) is a highly soluble and natively unfolded protein that binds to microtubules within neurons. Its dysfunction and aggregation into insoluble paired helical filaments is involved in the pathogenesis of Alzheimer’s disease (AD), constituting, together with accumulated {\ss}-amyloid (A{\ss}) peptides, a hallmark of the disease. Deciphering both the loss-of-function and toxic gain-of-function of hTau proteins is crucial to further understand the mechanisms leading to neurodegeneration in AD. As the fruit fly Drosophila melanogaster expresses Tau proteins (dTau) that are homologous to hTau, we aimed to better comprehend dTau functions by generating a specific tau knock-out (KO) fly line using homologous recombination. We observed that the specific removal of endogenous dTau proteins did not lead to overt, macroscopic phenotypes in flies. Indeed, survival, climbing ability and neuronal function were unchanged in tau KO flies. In addition, we did not find any overt positive or negative effect of dTau removal on human A{\ss}-induced toxicity. Altogether, our results indicate that the absence of dTau proteins has no major functional impact on flies, and suggests that our tau KO strain is a relevant model to further investigate the role of dTau proteins in vivo, thereby giving additional insights into hTau functions.",
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Burnouf, S, Grönke, S, Augustin, H, Dols, J, Gorsky, MK, Werner, J, Kerr, F, Alic, N, Martinez, P & Partridge, L 2016, 'Deletion of endogenous Tau proteins is not detrimental in Drosophila', Scientific Reports, vol. 6. https://doi.org/10.1038/srep23102

Deletion of endogenous Tau proteins is not detrimental in Drosophila. / Burnouf, Sylvie; Grönke, Sebastian; Augustin, Hrvoje; Dols, Jacqueline; Gorsky, Marianna Karina; Werner, Jennifer; Kerr, Fiona; Alic, Nazif; Martinez, Pedro; Partridge, Linda.

In: Scientific Reports, Vol. 6, 15.03.2016.

Research output: Contribution to journalArticle

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T1 - Deletion of endogenous Tau proteins is not detrimental in Drosophila

AU - Burnouf, Sylvie

AU - Grönke, Sebastian

AU - Augustin, Hrvoje

AU - Dols, Jacqueline

AU - Gorsky, Marianna Karina

AU - Werner, Jennifer

AU - Kerr, Fiona

AU - Alic, Nazif

AU - Martinez, Pedro

AU - Partridge, Linda

N1 - Acceptance from VoR

PY - 2016/3/15

Y1 - 2016/3/15

N2 - Human Tau (hTau) is a highly soluble and natively unfolded protein that binds to microtubules within neurons. Its dysfunction and aggregation into insoluble paired helical filaments is involved in the pathogenesis of Alzheimer’s disease (AD), constituting, together with accumulated ß-amyloid (Aß) peptides, a hallmark of the disease. Deciphering both the loss-of-function and toxic gain-of-function of hTau proteins is crucial to further understand the mechanisms leading to neurodegeneration in AD. As the fruit fly Drosophila melanogaster expresses Tau proteins (dTau) that are homologous to hTau, we aimed to better comprehend dTau functions by generating a specific tau knock-out (KO) fly line using homologous recombination. We observed that the specific removal of endogenous dTau proteins did not lead to overt, macroscopic phenotypes in flies. Indeed, survival, climbing ability and neuronal function were unchanged in tau KO flies. In addition, we did not find any overt positive or negative effect of dTau removal on human Aß-induced toxicity. Altogether, our results indicate that the absence of dTau proteins has no major functional impact on flies, and suggests that our tau KO strain is a relevant model to further investigate the role of dTau proteins in vivo, thereby giving additional insights into hTau functions.

AB - Human Tau (hTau) is a highly soluble and natively unfolded protein that binds to microtubules within neurons. Its dysfunction and aggregation into insoluble paired helical filaments is involved in the pathogenesis of Alzheimer’s disease (AD), constituting, together with accumulated ß-amyloid (Aß) peptides, a hallmark of the disease. Deciphering both the loss-of-function and toxic gain-of-function of hTau proteins is crucial to further understand the mechanisms leading to neurodegeneration in AD. As the fruit fly Drosophila melanogaster expresses Tau proteins (dTau) that are homologous to hTau, we aimed to better comprehend dTau functions by generating a specific tau knock-out (KO) fly line using homologous recombination. We observed that the specific removal of endogenous dTau proteins did not lead to overt, macroscopic phenotypes in flies. Indeed, survival, climbing ability and neuronal function were unchanged in tau KO flies. In addition, we did not find any overt positive or negative effect of dTau removal on human Aß-induced toxicity. Altogether, our results indicate that the absence of dTau proteins has no major functional impact on flies, and suggests that our tau KO strain is a relevant model to further investigate the role of dTau proteins in vivo, thereby giving additional insights into hTau functions.

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Burnouf S, Grönke S, Augustin H, Dols J, Gorsky MK, Werner J et al. Deletion of endogenous Tau proteins is not detrimental in Drosophila. Scientific Reports. 2016 Mar 15;6. https://doi.org/10.1038/srep23102