Tau protein- induced sequestration of the eukaryotic ribosome: Implications in neurodegenerative disease

• Published in: Scientific reports 2020-03, Vol.10 (1), p.5225-5225, Article 5225
• Main Authors: Banerjee, Senjuti, Ferdosh, Sehnaz, Ghosh, Amar Nath, Barat, Chandana
• Format: Article
• Language: English
• Subjects: 631/337; 631/45; Aggregates; Alzheimer's disease; Anions - chemistry; Anions - metabolism; Cytotoxicity; Disease; HeLa Cells; Heparin; Heparin - metabolism; Humanities and Social Sciences; Humans; Incubation; Microtubules - metabolism; multidisciplinary; Neurodegenerative diseases; Neurodegenerative Diseases - metabolism; Polyanions; Protein Domains; Protein interaction; Proteins; Ribosome Subunits, Large, Eukaryotic - metabolism; Ribosomes - metabolism; RNA, Transfer - metabolism; rRNA; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Science; Science (multidisciplinary); Tau protein; tau Proteins - chemistry; tau Proteins - genetics; tau Proteins - metabolism; Translation; tRNA; Yeasts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-61777-7

The human tau is a microtubule-associated intrinsically unstructured protein that forms intraneuronal cytotoxic deposits in neurodegenerative diseases, like tauopathies. Recent studies indicate that in Alzheimer’s disease, ribosomal dysfunction might be a crucial event in the disease pathology. Our earlier studies had demonstrated that amorphous protein aggregation in the presence of ribosome can lead to sequestration of the ribosomal components. The present study aims at determining the effect of incubation of the full-length tau protein (Ht40) and its microtubule binding 4-repeat domain (K18) on the eukaryotic ribosome. Our in vitro studies show that incubation of Ht40 and the K18 tau variants with isolated non-translating yeast ribosome can induce a loss of ribosome physical integrity resulting in formation of tau-rRNA-ribosomal protein aggregates. Incubation with the tau protein variants also led to a disappearance of the peak indicating the ribosome profile of the HeLa cell lysate and suppression of translation in the human in vitro translation system. The incubation of tau protein with the ribosomal RNA leads to the formation of tau-rRNA aggregates. The effect of K18 on the yeast ribosome can be mitigated in the presence of cellular polyanions like heparin and tRNA, thereby indicating the electrostatic nature of the aggregation process.