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Decreased synthesis of ribosomal proteins in tauopathy revealed by non‐canonical amino acid labelling
Author(s) -
Evans Harrison Tudor,
Benetatos Joseph,
van Roijen Marloes,
Bodea LiviuGabriel,
Götz Jürgen
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2018101174
Subject(s) - tauopathy , research centre , dementia , library science , history , art history , medicine , pathology , computer science , neurodegeneration , disease
Abstract Tau is a scaffolding protein that serves multiple cellular functions that are perturbed in neurodegenerative diseases, including Alzheimer's disease ( AD ) and frontotemporal dementia ( FTD ). We have recently shown that amyloid‐β, the second hallmark of AD , induces de novo protein synthesis of tau. Importantly, this activation was found to be tau‐dependent, raising the question of whether FTD ‐tau by itself affects protein synthesis. We therefore applied non‐canonical amino acid labelling to visualise and identify newly synthesised proteins in the K369I tau transgenic K3 mouse model of FTD . This revealed massively decreased protein synthesis in neurons containing pathologically phosphorylated tau, a finding confirmed in P301L mutant tau transgenic rT g4510 mice. Using quantitative SWATH ‐ MS proteomics, we identified changes in 247 proteins of the de novo proteome of K3 mice. These included decreased synthesis of the ribosomal proteins RPL 23, RPLP 0, RPL 19 and RPS 16, a finding that was validated in both K3 and rT g4510 mice. Together, our findings present a potential pathomechanism by which pathological tau interferes with cellular functions through the dysregulation of ribosomal protein synthesis.