Hsp90 and its co-chaperone Sti1 control TDP-43 misfolding and toxicity
| Autor: | Marilene H. Lopes, Lilian Tsai-Wei Lin, Marco A. M. Prado, Abdul Razzaq, Soojie Hong, Martin L. Duennwald, Brendan Charles, Flavio H. Beraldo, Sonja E. Di Gregorio, Vania F. Prado |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Protein Folding Apoptosis Saccharomyces cerevisiae Protein aggregation Biochemistry Mice 03 medical and health sciences 0302 clinical medicine mental disorders Genetics medicine Animals Humans HSP90 Heat-Shock Proteins Amyotrophic lateral sclerosis Molecular Biology Heat-Shock Proteins Inclusion Bodies Mice Knockout Neurons Binding Sites biology Chemistry nutritional and metabolic diseases medicine.disease Hsp90 nervous system diseases 3. Good health Cell biology DNA-Binding Proteins Mice Inbred C57BL Co-chaperone 030104 developmental biology TDP-43 Proteinopathies Toxicity TOXICIDADE EM ANIMAL biology.protein Female Protein folding 030217 neurology & neurosurgery Function (biology) HeLa Cells Biotechnology |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Protein misfolding is a central feature of most neurodegenerative diseases. Molecular chaperones can modulate the toxicity associated with protein misfolding, but it remains elusive which molecular chaperones and co-chaperones interact with specific misfolded proteins. TDP-43 misfolding and inclusion formation are a hallmark of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. Using yeast and mammalian neuronal cells we find that Hsp90 and its co-chaperone Sti1 have the capacity to alter TDP-43 misfolding, inclusion formation, aggregation, and cellular toxicity. Our data also demonstrate that impaired Hsp90 function sensitizes cells to TDP-43 toxicity and that Sti1 specifically interacts with and strongly modulates TDP-43 toxicity in a dose-dependent manner. Our study thus uncovers a previously unrecognized tie between Hsp90, Sti1, TDP-43 misfolding, and cellular toxicity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|