HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells
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- Haiyang Yu
- Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, USA.
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- Shan Lu
- Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, USA.
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- Kelsey Gasior
- Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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- Digvijay Singh
- Division of Biological Sciences, University of California, San Diego, San Diego, CA, USA.
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- Sonia Vazquez-Sanchez
- Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, USA.
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- Olga Tapia
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
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- Divek Toprani
- Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, USA.
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- Melinda S. Beccari
- Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, USA.
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- John R. Yates
- Departments of Molecular Medicine and Neurobiology, The Scripps Research Institute, La Jolla, CA, USA.
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- Sandrine Da Cruz
- Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, USA.
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- Jay M. Newby
- Department of Mathematical and Statistical Sciences, University of Alberta, Edmonton, Alberta, Canada.
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- Miguel Lafarga
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
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- Amy S. Gladfelter
- Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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- Elizabeth Villa
- Division of Biological Sciences, University of California, San Diego, San Diego, CA, USA.
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- Don W. Cleveland
- Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, USA.
説明
<jats:title>The makings of anisosomes</jats:title> <jats:p> Phase separation of proteins within the cell can produce a liquid-inside-a-liquid phase resembling oil droplets in water. Yu <jats:italic>et al.</jats:italic> 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. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" related-article-type="in-this-issue" xlink:href="10.1126/science.abb4309">eabb4309</jats:related-article> </jats:p>
収録刊行物
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- Science
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Science 371 (6529), eabb4309-, 2021-02-05
American Association for the Advancement of Science (AAAS)