Open AccessHSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells
Author(s) -
Haiyang Yu,
Shan Lu,
Kelsey Gasior,
Digvijay Singh,
Sonia Vázquez-Sánchez,
O. Tapia,
Divek Toprani,
Melinda S. Beccari,
John R. Yates,
Sandrine Da Cruz,
Jay Newby,
Miguel Lafarga,
Amy S. Gladfelter,
Elizabeth Villa,
Don W. Cleveland
Publication year - 2021
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.abb4309
Subject(s) - rna , neurodegeneration , stress granule , proteasome , cytoplasm , chemistry , biophysics , acetylation , adenosine triphosphate , microbiology and biotechnology , biochemistry , biology , messenger rna , medicine , disease , translation (biology) , pathology , gene
The makings of anisosomes Phase separation of proteins within the cell can produce a liquid-inside-a-liquid phase resembling oil droplets in water. Yuet 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
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom