Altered ribosomal function and protein synthesis caused by tau
Abstract The synthesis of new proteins is a fundamental aspect of cellular life and is required for many neurological processes, including the formation, updating and extinction of long-term memories. Protein synthesis is impaired in neurodegenerative diseases including tauopathies, in which patholo...
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doaj-4127815f43ac4aa0bd01fb124c002f622021-06-20T11:29:33ZengBMCActa Neuropathologica Communications2051-59602021-06-019111410.1186/s40478-021-01208-4Altered ribosomal function and protein synthesis caused by tauHarrison Tudor Evans0Deonne Taylor1Andrew Kneynsberg2Liviu-Gabriel Bodea3Jürgen Götz4Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandAbstract The synthesis of new proteins is a fundamental aspect of cellular life and is required for many neurological processes, including the formation, updating and extinction of long-term memories. Protein synthesis is impaired in neurodegenerative diseases including tauopathies, in which pathology is caused by aberrant changes to the microtubule-associated protein tau. We recently showed that both global de novo protein synthesis and the synthesis of select ribosomal proteins (RPs) are decreased in mouse models of frontotemporal dementia (FTD) which express mutant forms of tau. However, a comprehensive analysis of the effect of FTD-mutant tau on ribosomes is lacking. Here we used polysome profiling, de novo protein labelling and mass spectrometry-based proteomics to examine how ribosomes are altered in models of FTD. We identified 10 RPs which were decreased in abundance in primary neurons taken from the K3 mouse model of FTD. We further demonstrate that expression of human tau (hTau) decreases both protein synthesis and biogenesis of the 60S ribosomal subunit, with these effects being exacerbated in the presence of FTD-associated tau mutations. Lastly, we demonstrate that expression of the amino-terminal projection domain of hTau is sufficient to reduce protein synthesis and ribosomal biogenesis. Together, these data reinforce a role for tau in impairing ribosomal function.https://doi.org/10.1186/s40478-021-01208-4FTDNeurodegenerationPolysome profilingProtein synthesisRibosomesTau |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Harrison Tudor Evans Deonne Taylor Andrew Kneynsberg Liviu-Gabriel Bodea Jürgen Götz |
spellingShingle |
Harrison Tudor Evans Deonne Taylor Andrew Kneynsberg Liviu-Gabriel Bodea Jürgen Götz Altered ribosomal function and protein synthesis caused by tau Acta Neuropathologica Communications FTD Neurodegeneration Polysome profiling Protein synthesis Ribosomes Tau |
author_facet |
Harrison Tudor Evans Deonne Taylor Andrew Kneynsberg Liviu-Gabriel Bodea Jürgen Götz |
author_sort |
Harrison Tudor Evans |
title |
Altered ribosomal function and protein synthesis caused by tau |
title_short |
Altered ribosomal function and protein synthesis caused by tau |
title_full |
Altered ribosomal function and protein synthesis caused by tau |
title_fullStr |
Altered ribosomal function and protein synthesis caused by tau |
title_full_unstemmed |
Altered ribosomal function and protein synthesis caused by tau |
title_sort |
altered ribosomal function and protein synthesis caused by tau |
publisher |
BMC |
series |
Acta Neuropathologica Communications |
issn |
2051-5960 |
publishDate |
2021-06-01 |
description |
Abstract The synthesis of new proteins is a fundamental aspect of cellular life and is required for many neurological processes, including the formation, updating and extinction of long-term memories. Protein synthesis is impaired in neurodegenerative diseases including tauopathies, in which pathology is caused by aberrant changes to the microtubule-associated protein tau. We recently showed that both global de novo protein synthesis and the synthesis of select ribosomal proteins (RPs) are decreased in mouse models of frontotemporal dementia (FTD) which express mutant forms of tau. However, a comprehensive analysis of the effect of FTD-mutant tau on ribosomes is lacking. Here we used polysome profiling, de novo protein labelling and mass spectrometry-based proteomics to examine how ribosomes are altered in models of FTD. We identified 10 RPs which were decreased in abundance in primary neurons taken from the K3 mouse model of FTD. We further demonstrate that expression of human tau (hTau) decreases both protein synthesis and biogenesis of the 60S ribosomal subunit, with these effects being exacerbated in the presence of FTD-associated tau mutations. Lastly, we demonstrate that expression of the amino-terminal projection domain of hTau is sufficient to reduce protein synthesis and ribosomal biogenesis. Together, these data reinforce a role for tau in impairing ribosomal function. |
topic |
FTD Neurodegeneration Polysome profiling Protein synthesis Ribosomes Tau |
url |
https://doi.org/10.1186/s40478-021-01208-4 |
work_keys_str_mv |
AT harrisontudorevans alteredribosomalfunctionandproteinsynthesiscausedbytau AT deonnetaylor alteredribosomalfunctionandproteinsynthesiscausedbytau AT andrewkneynsberg alteredribosomalfunctionandproteinsynthesiscausedbytau AT liviugabrielbodea alteredribosomalfunctionandproteinsynthesiscausedbytau AT jurgengotz alteredribosomalfunctionandproteinsynthesiscausedbytau |
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1721369973890220032 |