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  A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation

Patel, A., Lee, H. O., Jawerth, L., Maharana, S., Jahnel, M., Hein, M. Y., et al. (2015). A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation. CELL, 162(5), 1066-1077. doi:10.1016/j.cell.2015.07.047.

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 Creators:
Patel, Avinash1, Author
Lee, Hyun O.1, Author
Jawerth, Louise1, Author
Maharana, Shovamayee1, Author
Jahnel, Marcus1, Author
Hein, Marco Y.2, Author              
Stoynov, Stoyno1, Author
Mahamid, Julia3, Author              
Saha, Shambaditya1, Author
Franzmann, Titus M.1, Author
Pozniakovski, Andrej1, Author
Poser, Ina1, Author
Maghelli, Nicola1, Author
Royer, Loic A.1, Author
Weigert, Martin1, Author
Myers, Eugene W.1, Author
Grill, Stephan1, Author
Drechsel, David1, Author
Hyman, Anthony A.1, Author
Alberti, Simon1, Author
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
3Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565142              

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Free keywords: AMYOTROPHIC-LATERAL-SCLEROSIS; RNA-BINDING PROTEINS; PRION-LIKE DOMAINS; BEAM PLANE ILLUMINATION; CELL-FREE FORMATION; DNA-DAMAGE; STRESS GRANULES; NEURODEGENERATIVE DISEASES; POLYMERASE-II; SEPARATION
 Abstract: Many proteins contain disordered regions of low-sequence complexity, which cause aging-associated diseases because they are prone to aggregate. Here, we study FUS, a prion-like protein containing intrinsically disordered domains associated with the neurodegenerative disease ALS. We show that, in cells, FUS forms liquid compartments at sites of DNA damage and in the cytoplasm upon stress. We confirm this by reconstituting liquid FUS compartments in vitro. Using an in vitro "aging'' experiment, we demonstrate that liquid droplets of FUS protein convert with time from a liquid to an aggregated state, and this conversion is accelerated by patient-derived mutations. We conclude that the physiological role of FUS requires forming dynamic liquid-like compartments. We propose that liquid-like compartments carry the trade-off between functionality and risk of aggregation and that aberrant phase transitions within liquid-like compartments lie at the heart of ALS and, presumably, other age-related diseases.

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Language(s): eng - English
 Dates: 2015
 Publication Status: Published in print
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: CELL
Source Genre: Journal
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Publ. Info: 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA : CELL PRESS
Pages: - Volume / Issue: 162 (5) Sequence Number: - Start / End Page: 1066 - 1077 Identifier: ISSN: 0092-8674