HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells
| Autor: | Digvijay Singh, Kelsey Gasior, Shan Lu, Olga Tapia, Amy S. Gladfelter, Elizabeth Villa, Don W. Cleveland, John R. Yates, Sandrine Da Cruz, Melinda S. Beccari, Divek Toprani, Jay M. Newby, Haiyang Yu, Miguel Lafarga, Sonia Vazquez-Sanchez |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Aging Proteasome Endopeptidase Complex Protein domain RNA-binding protein Protein aggregation Histone Deacetylases Article Rats Sprague-Dawley Mice Protein Aggregates 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Protein Domains Animals Humans HSP70 Heat-Shock Proteins Neurons Multidisciplinary Chemistry Cryoelectron Microscopy RNA-Binding Proteins RNA Neurodegenerative Diseases Liquid Crystals Rats DNA-Binding Proteins Mice Inbred C57BL HEK293 Cells 030104 developmental biology Proteasome Cytoplasm Acetylation Mutation Biophysics Anisotropy Proteasome Inhibitors Adenosine triphosphate 030217 neurology & neurosurgery |
| Zdroj: | Science |
| ISSN: | 1095-9203 0036-8075 |
| DOI: | 10.1126/science.abb4309 |
| Popis: | The makings of anisosomes Phase separation of proteins within the cell can produce a liquid-inside-a-liquid phase resembling oil droplets in water. Yu et al. now report that an RNA-binding protein called TDP-43, in which mutation and aggregation are linked to amyotrophic lateral sclerosis and frontotemporal dementia, phase separates into complex droplets, which they named anisosomes. This process occurred when TDP-43 lost its ability to bind RNA through disease-causing mutation or posttranslational acetylation. Anisosomes have spherical shells of TDP-43 (with properties of a liquid crystal) surrounding centers of the protein chaperone HSP70. Chaperone activity was required to maintain liquidity. Anisosomes formed in neurons in vivo when proteasome activity was inhibited and were converted into aggregates when adenosine triphosphate (ATP) levels fell. Science , this issue p. eabb4309 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|