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

Liangzhong Lim, Yuanyuan Wei, Yimei Lu, Jianxing Jikui Song, Jae Kyo Jeong, Jae Suk Seo, Myung Hee Moon, You Jin Lee, Jae Won Seol, Sang Youel Park, Florent Laferrière, Zuzanna Maniecka, Manuela Pérez-Berlanga, Marian Hruska-Plochan, Larissa Gilhespy, Eva Maria Hock, Ulrich Wagner, Tariq Afroz, Paul J. Boersema, Gery BarmettlerSandrine C. Foti, Yasmine T. Asi, Adrian M. Isaacs, Ashraf Al-Amoudi, Amanda Lewis, Henning Stahlberg, John Ravits, Francesca De Giorgi, François Ichas, Erwan Bezard, Paola Picotti, Tammaryn Lashley, Magdalini Polymenidou, Alexander E. Conicella, Gül H. Zerze, Jeetain Mittal, Nicolas L. Fawzi, Avinash Patel, Hyun O. Lee, Louise Jawerth, Shovamayee Maharana, Marcus Jahnel, Marco Y. Hein, Stoyno Stoynov, Julia Mahamid, Shambaditya Saha, Titus M. Franzmann, Andrej Pozniakovski, Ina Poser, Nicola Maghelli, Loic A. Royer, Martin Weigert, Eugene W. Myers, Stephan Grill, David Drechsel, Anthony A. Hyman, Simon Alberti, Archana Prasad, Vidhya Bharathi, Vishwanath Sivalingam, Amandeep Girdhar, Basant K. Patel, Anthony Khong, Tyler Matheny, Saumya Jain, Sarah F. Mitchell, Joshua R. Wheeler, Roy Parker, Taylor D. Pobran, Lauren M. Forgrave, Yu Zi Zheng, John G.K. Lim, Ian R.A. Mackenzie, Mari L. DeMarco, Jeannie Chew, Casey Cook, Tania F. Gendron, Karen Jansen-West, Giulia Del Rosso, Lillian M. Daughrity, Monica Castanedes-Casey, Aishe Kurti, Jeannette N. Stankowski, Matthew D. Disney, Jeffrey D. Rothstein, Dennis W. Dickson, John D. Fryer, Yong Jie Yun wu Zhang, Leonard Petrucelli, Sílvia Porta, Yan Xu, Clark R. Restrepo, Linda K. Kwong, Bing Zhang, Hannah J. Brown, Edward B. Lee, John Q. Trojanowski, Virginia M.Y. Lee, Tomohiro Ishii, Emiko Kawakami, Kentaro Endo, Hidemi Misawa, Kazuhiko Watabe, Elizabeth L. Guenther, Peng Ge, Hamilton Trinh, Michael R. Sawaya, Duilio Cascio, David R. Boyer, Tamir Gonen, Z. Hong Zhou, David S. Eisenberg, Steven Boeynaems, Aaron D. Gitler, Miguel F. Sanmamed, Lieping Chen, Raviv Pryluk, Yoav Kfir, Hagar Gelbard-Sagiv, Itzhak Fried, Rony Paz, Laura M. Wingler, Matthias Elgeti, Daniel Hilger, Naomi R. Latorraca, Michael T. Lerch, Dean P. Staus, Ron O. Dror, Brian K. Kobilka, Wayne L. Hubbell, Robert J. Lefkowitz, Pablo Baeza-Centurion, Belén Miñana, Jörn M. Schmiedel, Juan Valcárcel, Ben Lehner, Simon Alberti, Amy Gladfelter, Tanja Mittag, Xiaoting Xiang Li, Tian Hua, Kiran Vemuri, Jo Hao Ho, Yiran Wu, Lijie Wu, Petr Popov, Othman Benchama, Nikolai Zvonok, K'ara Locke, Lu Qu, Gye Won Han, Malliga R. Iyer, Resat Cinar, Nathan J. Coffey, Jingjing Wang, Meng Wu, Vsevolod Katritch, Suwen Zhao, George Kunos, Laura M. Bohn, Alexandros Makriyannis, Raymond C. Stevens, Zhijie Jie Liu, Laura M. Wingler, Conor McMahon, Dean P. Staus, Robert J. Lefkowitz, Andrew C. Kruse, Michael A. Wheeler, Merja Jaronen, Ruxandra Covacu, Stephanie E.J. Zandee, Giulia Scalisi, Veit Rothhammer, Emily C. Tjon, Chun Cheih Chao, Jessica E. Kenison, Manon Blain, Vijayaraghava T.S. Rao, Patrick Hewson, Andreia Barroso, Cristina Gutiérrez-Vázquez, Alexandre Prat, Jack P. Antel, Russ Hauser, Francisco J. Quintana, Edoardo Pasolli, Francesco Asnicar, Serena Manara, Moreno Zolfo, Nicolai Karcher, Federica Armanini, Francesco Beghini, Paolo Manghi, Adrian Tett, Paolo Ghensi, Maria Carmen Collado, Benjamin L. Rice, Casey DuLong, Xochitl C. Morgan, Christopher D. Golden, Christopher Quince, Curtis Huttenhower, Nicola Segata, Shuo Liu, Simone Hausmann, Scott Moore Carlson, Mary Esmeralda Fuentes, Joel William Francis, Renjitha Pillai, Shane Michael Lofgren, Laura Hulea, Kristofferson Tandoc, Jiuwei Lu, Ami Angela Li, Nicholas Dang Nguyen, Marcello Caporicci, Michael Paul Kim, Anirban Maitra, Huamin Wang, Ignacio Ivan Wistuba, John Anthony Porco, Michael Cory Bassik, Joshua Eric Elias, Jianxing Jikui Song, Ivan Topisirovic, Capucine Van Rechem, Pawel Karol Mazur, Or Gozani, Viviana I. Risca, Sung Hwan Moon, Chun Hao Huang, Shauna L. Houlihan, Kausik Regunath, William A. Freed-Pastor, John P. Morris, Darjus F. Tschaharganeh, Edward R. Kastenhuber, Anthony M. Barsotti, Rachel Culp-Hill, Wen Xue, Yu Jui Ho, Timour Baslan, Xiaoting Xiang Li, Allison Mayle, Elisa de Stanchina, Lars Zender, David R. Tong, Angelo D'Alessandro, Scott W. Lowe, Carol Prives, Emily Lorenzen, Thomas P. Sakmar, Olga L. Rojas, Anne Katrin Pröbstel, Elisa A. Porfilio, Angela A. Wang, Marc Charabati, Tian Sun, Dennis S.W. Lee, Georgina Galicia, Valeria Ramaglia, Lesley A. Ward, Leslie Y.T. Leung, Ghazal Najafi, Khashayar Khaleghi, Beatriz Garcillán, Ami Angela Li, Rickvinder Besla, Ikbel Naouar, Eric Y. Cao, Pailin Chiaranunt, Kyle Burrows, Hannah G. Robinson, Jessica R. Allanach, Jennifer Yam, Helen Luck, Daniel J. Campbell, David Allman, David G. Brooks, Michio Tomura, Ryan Baumann, Scott S. Zamvil, Amit Bar-Or, Marc S. Horwitz, Daniel A. Winer, Arthur Mortha, Fabienne Mackay, Alexandre Prat, Lisa C. Osborne, Clinton Robbins, Sergio E. Baranzini, Jennifer L. Gommerman, Xinlu Wang, Yifang Xuan, Yuling Han, Xiang Ding, Kai Ye, Fuquan Yang, Pu Gao, Stephen P. Goff, Guangxia Gao, Thomas Korn, Kaavya Krishna Kumar, Moran Shalev-Benami, Michael J. Robertson, Hongli Hu, Samuel D. Banister, Scott A. Hollingsworth, Naomi R. Latorraca, Hideaki E. Kato, Daniel Hilger, Shoji Maeda, William I. Weis, David L. Farrens, Ron O. Dror, Sanjay V. Malhotra, Brian K. Kobilka, Georgios Skiniotis, Masae Ohno, Tadashi Ando, David G. Priest, Vipin Kumar, Yamato Yoshida, Yuichi Taniguchi, Suying Bao, Daniel F. Moakley, Chaolin Zhang, Ron D. Jachimowicz, Filippo Beleggia, Jörg Isensee, Bhagya Bhavana Velpula, Jonas Goergens, Matias A. Bustos, Markus A. Doll, Anjana Shenoy, Cintia Checa-Rodriguez, Janica Lea Wiederstein, Keren Baranes-Bachar, Christoph Bartenhagen, Falk Hertwig, Nizan Teper, Tomohiko Nishi, Anna Schmitt, Felix Distelmaier, Hermann Josef Lüdecke, Beate Albrecht, Marcus Krüger, Björn Schumacher, Tamar Geiger, Dave S.B. Hoon, Pablo Huertas, Matthias Fischer, Tim Hucho, Martin Peifer, Yael Ziv, H. Christian Reinhardt, Dagmar Wieczorek, Yosef Shiloh, Peter A. Audano, Arvis Sulovari, Tina A. Graves-Lindsay, Stuart Cantsilieris, Melanie Sorensen, Anne Marie E. Welch, Max L. Dougherty, Bradley J. Nelson, Ankeeta Shah, Susan K. Dutcher, Wesley C. Warren, Vincent Magrini, Sean D. McGrath, Yang I. Li, Richard K. Wilson, Evan E. Eichler, Bing Zhang, Jun Li, Xiaolin Xiaobao Xiuna Yang, Lijie Wu, Jia Zhang, Yang Yang, Yao Zhao, Lu Zhang, Xiaolin Xiaobao Xiuna Yang, Xiaolin Xiaobao Xiuna Yang, Xi Cheng, Zhijie Jie Liu, Biao Jiang, Hualiang Jiang, Luke W. Guddat, Haitao Yang, Zihe Rao, Michael D. Vahey, Daniel A. Fletcher, Kishore Jaganathan, Sofia Kyriazopoulou Panagiotopoulou, Jeremy F. McRae, Siavash Fazel Darbandi, David Knowles, Yang I. Li, Jack A. Kosmicki, Juan Arbelaez, Wenwu Cui, Grace B. Schwartz, Eric D. Chow, Efstathios Kanterakis, Hong Gao, Amirali Kia, Serafim Batzoglou, Stephan J. Sanders, Kyle Kai How Farh, Sebastiaan De Schepper, Simon Verheijden, Javier Aguilera-Lizarraga, Maria Francesca Viola, Werend Boesmans, Nathalie Stakenborg, Iryna Voytyuk, Inga Schmidt, Bram Boeckx, Isabelle Dierckx de Casterlé, Veerle Baekelandt, Erika Gonzalez Dominguez, Matthias Mack, Inge Depoortere, Bart De Strooper, Ben Sprangers, Uwe Himmelreich, Stefaan Soenen, Martin Guilliams, Pieter Vanden Berghe, Elizabeth Jones, Diether Lambrechts, Guy Boeckxstaens, Jonathan J. Ruprecht, Martin S. King, Thomas Zögg, Antoniya A. Aleksandrova, Els Pardon, Paul G. Crichton, Jan Steyaert, Edmund R.S. Kunji, Chiara Foglieni, Stéphanie Papin, Agnese Salvadè, Tariq Afroz, Sandra Pinton, Giona Pedrioli, Giorgio Ulrich, Magdalini Polymenidou, Paolo Paganetti, Fuyuki Kametani, Tomokazu Obi, Takeo Shishido, Hiroyasu Akatsu, Shigeo Murayama, Yuko Saito, Mari Yoshida, Masato Hasegawa, Phoebe S. Tsoi, Kyoung Jae Choi, Paul G. Leonard, Antons Sizovs, Mahdi Muhammad Moosa, Kevin R. MacKenzie, Josephine C. Ferreon, Allan Chris M. Ferreon, Elsa Zacco, Ricardo Graña-Montes, Stephen R. Martin, Natalia Sanchez de Groot, Caterina Alfano, Gian Gaetano Tartaglia, Annalisa Pastore, Hao Ru Li, Wan Chin Chiang, Po Chun Chou, Won Jing Wang, Jie rong Huang, Gonçalo C. Pereira, William J. Allen, Daniel W. Watkins, Lisa Buddrus, Dylan Noone, Xia Liu, Andrew P. Richardson, Agnieszka Chacinska, Ian Collinson, Emma L. Scotter, Han Jou Chen, Christopher E. Shaw, David Roulois, Helen Loo Yau, Rajat Singhania, Yadong Wang, Arnavaz Danesh, Shu Yi Shen, Han Han, Gangning Liang, Peter A. Jones, Trevor J. Pugh, Catherine O'Brien, Daniel D. De Carvalho, Sandro Orrù, Paola Coni, Andrea Floris, Roberto Littera, Carlo Carcassi, Valeria Sogos, Carla Brancia, Miguel Mompeán, Marco Baralle, Emanuele Buratti, Douglas V. Laurents, Leeanne McGurk, Edward Gomes, Lin Guo, Jelena Mojsilovic-Petrovic, Van Tran, Robert G. Kalb, James Shorter, Nancy M. Bonini, Clotilde Lagier-Tourenne, Don W. Cleveland, Benjamin M Schwenk, Hannelore Hartmann, Alperen Serdaroglu, Martin H Schludi, Daniel Hornburg, Felix Meissner, Denise Orozco, Alessio Colombo, Sabina Tahirovic, Meike Michaelsen, Franziska Schreiber, Simone Haupt, Michael Peitz, Oliver Brüstle, Clemens Küpper, Thomas Klopstock, Markus Otto, Albert C Ludolph, Thomas Arzberger, Peer‐Hendrik Kuhn, Dieter Edbauer, Anastassios Vourekas, Zissimos Mourelatos, Laetitia Miguel, Tracey Avequin, Morgane Delarue, Sébastien Feuillette, Thierry Frébourg, Dominique Campion, Magalie Lecourtois, Minh Bao Huynh, Joao Villares, Julia Elisa Sepúlveda Díaz, Stephy Christiaans, Gilles Carpentier, Mohand Ouidir Ouidja, Ludmilla Sissoeff, Rita Raisman-Vozari, Dulce Papy-Garcia, Xiumei Huang, Yaomin Chen, Han Zhang, Qilin Ma, Yong Jie Yun wu Zhang, Huaxi Xu, Simon Alberti, Amy Gladfelter, Tanja Mittag

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Evidence is now mounting that liquid-liquid phase separation (LLPS) underlies the formation of membraneless compartments in cells. This realization has motivated major efforts to delineate the function of such biomolecular condensates in normal cells and their roles in contexts ranging from development to age-related disease. There is great interest in understanding the underlying biophysical principles and the specific properties of biological condensates with the goal of bringing insights into a wide range of biological processes and systems. The explosion of physiological and pathological contexts involving LLPS requires clear standards for their study. Here, we propose guidelines for rigorous experimental characterization of LLPS processes in vitro and in cells, discuss the caveats of common experimental approaches, and point out experimental and theoretical gaps in the field.
Original languageAmerican English
Title of host publicationCell
Pages1-15
Number of pages15
StatePublished - 2019

Publication series

NameCell
Volume33

Keywords

  • ABCA1
  • ALS
  • ALS therapeutics
  • ARB
  • Aging
  • Alzheimer's disease
  • Amyotrophic lateral sclerosis
  • Amyotrophic lateral sclerosis (ALS)
  • B cells
  • C9ORF72
  • C9orf72
  • CB1
  • DEER
  • DNA damage
  • DNA double-strand break repair
  • Drosophila
  • EAE
  • Endocytosis
  • Extracellular matrix
  • FTD
  • FUS
  • Frontotemporal dementia
  • Frontotemporal lobar degeneration
  • Frontotemporal lobar degeneration (FTLD)
  • Fubinaca
  • G protein-coupled receptor
  • G-protein coupled receptor
  • GPCR
  • Gag-Pol
  • Gi
  • Glycosaminoglycans
  • Growth factors
  • HIF-1α
  • HIV-1
  • Heparan sulfate
  • Hippocampus
  • HnRNPs
  • Hyperstable H-bonds
  • Hypoxia
  • IRE1α
  • IgA
  • Liquid-liquid phase separation (LLPS)
  • METTL13
  • MS
  • Mitotoxicity
  • NF-κB
  • NanoLuc
  • Neurodegeneration
  • Neuron cell
  • PARP
  • PARylation
  • Pathological amyloids
  • Prion
  • Protein misfolding and disease
  • Proteinopathy
  • Prp106-126
  • RAS
  • RNA
  • RNA binding
  • RNA localization
  • RNA-seq
  • RNP granules
  • SREBP-2
  • Salubrinal
  • Sigmar1
  • Stress granules
  • TARDBP
  • TDP
  • TDP-43
  • Tankyrase
  • Transitive response DNA-bonding protein 43 kDa (TD
  • UBQLN4 deficiency syndrome
  • XBP1
  • adenine nucleotide translocase
  • adenine nucleotide translocator
  • alternating access mechanism
  • amygdala
  • amyotrophic lateral sclerosis
  • angiotensin II type 1 receptor
  • angiotensin receptor
  • angiotensin receptor blocker
  • anxiety/mood disorders
  • artificial intelligence
  • astrocyte
  • bacterial Sec system
  • beta-arrestin
  • biased agonism
  • bioenergetics
  • bongkrekate
  • cancer
  • cancer metabolism
  • cannabinoid receptor
  • cannabinoid receptor CB2
  • cardiolipin
  • cingulate-cortex
  • cognition
  • conformational selection
  • cryo-EM
  • crystal structure
  • deep learning
  • deep mutational scan
  • double electron-electron resonance spectroscopy
  • eCLIP
  • eEF1A
  • efficiency
  • epistasis
  • evolution
  • experimental autoimmune encephalomyelitis
  • frontotemporal dementia
  • functional selectivity
  • gap closure
  • genetic interactions
  • genetic prediction
  • genetics
  • genome instability syndrome
  • genotype-to-phenotype map
  • glia
  • heterotrimeric G protein
  • homologous recombination
  • host antiviral factor
  • human microbiome
  • human reference genome
  • induced fit
  • inflammation
  • ligand design
  • live assay
  • lung cancer
  • lysine methylation
  • mRNP assemblies
  • major allele
  • metagenomic assembly
  • metagenomic mappability
  • metagenomic meta-analysis
  • metagenomics
  • mevalonate pathway
  • microbiota
  • misfolding
  • mitochondria
  • mitochondrial protein import
  • molecular dynamics simulations
  • motor neuron disease
  • multiple sclerosis
  • mutation
  • nanobody
  • neural code
  • neurodegeneration
  • neurodegenerative diseases
  • non-Westernized microbiomes
  • non-homologous end joining
  • p53
  • pancreatic cancer
  • phosphorylation
  • plasma cells
  • poly(ADP-ribose)
  • premature translation termination
  • primates
  • programmed -1 ribosomal frameshifting
  • proteasomal degradation
  • protein aggregation
  • protein methylation
  • protein phase diagram
  • protein translocation
  • real-time (SMRT) sequencing
  • regulatory sequence
  • robustness
  • single molecule FISH
  • single-domain antibody
  • single-molecule
  • smFRET
  • small intestinal lamina propria
  • splice site
  • splicing
  • stress granule
  • stress granules
  • structural variation
  • subtype selectivity
  • synthetic cannabinoid
  • targeted cancer therapy
  • translation
  • translation elongation
  • translation recoding
  • transport mechanism
  • tumor suppression
  • ubiquitin
  • unexplored microbial diversity
  • whole-genome sequence and assembly
  • yeast display
  • zebrafish
  • β-amyloid

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