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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2015 (arch)     Display Documents



ID: 717999.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2015 (arch)
A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation.
Authors:Patel, Avinash; Lee, Hyun-Ok Kate; Jawerth, Louise; Maharana, Shovamayee; Jahnel, Marcus; Hein, Marco Y; Stoynov, Stoyno; Mahamid, J.; Saha, Shambaditya; Franzmann, Titus; Pozniakovski, Andrei; Poser, Ina; Maghelli, Nicola; Royer, Loic; Weigert, Martin; Myers, Eugene W; Grill, Stephan W.; Drechsel, David N.; Hyman, Anthony; Alberti, Simon
Date of Publication (YYYY-MM-DD):2015
Title of Journal:Cell
Volume:162
Issue / Number:5
Start Page:1066
End Page:1077
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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. VIDEO ABSTRACT.
External Publication Status:published
Document Type:Article
Communicated by:Thüm
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:6272
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