Journal ArticleDOI
ALS/FTLD-Linked Mutations in FUS Glycine Residues Cause Accelerated Gelation and Reduced Interactions with Wild-Type FUS.
Kevin Rhine,Monika A. Makurath,James Liu,James Liu,Sophie Skanchy,Christian Lopez,Kevin F. Catalan,Ye Ma,Charlotte M. Fare,James Shorter,Taekjip Ha,Yann R. Chemla,Sua Myong,Sua Myong +13 more
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TLDR
It is demonstrated that ALS/FTLD-linked FUS mutations in glycine (G) strikingly drive formation of droplets that do not readily interact withWT FUS, whereas arginine (R) mutants form mixed condensates with WT FUS.About:
This article is published in Molecular Cell.The article was published on 2020-11-19. It has received 62 citations till now.read more
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High-resolution, long-term characterization of bacterial motility using optical tweezers
TL;DR: In this paper, a single-cell motility assay is presented, which allows the quantification of bacterial swimming in a well-controlled environment, for durations of up to an hour and with a temporal resolution greater than the flagellar rotation rates of ∼100 Hz.
Journal ArticleDOI
FUS and TDP-43 Phases in Health and Disease.
TL;DR: This paper examined how sequence, structure, post-translational modifications, and RNA can affect the self-assembly of these RNA-binding proteins (RBPs) and discussed how their emerging understanding of FUS and TDP-43 liquid-liquid phase separation (LLPS) and aggregation, could be leveraged to design new therapies for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and limbic-predominant age-related TPD-43 encephalopathy (LATE).
Journal ArticleDOI
Combating deleterious phase transitions in neurodegenerative disease.
April L. Darling,James Shorter +1 more
TL;DR: Uversky et al. as discussed by the authors discuss the mechanisms by which aberrant protein phase transitions may contribute to neurodegenerative disease and outline potential therapeutic strategies to counter deleterious phases.
Journal ArticleDOI
Sequence Determinants of the Aggregation of Proteins Within Condensates Generated by Liquid-liquid Phase Separation.
TL;DR: The authors investigated the sequence determinants of aggregation via the condensation pathway, and identified three relevant features: droplet-promoting propensity, aggregation-enhancing propensity and multimodal interactions quantified by the binding mode entropy.
Journal ArticleDOI
Polyphasic linkage and the impact of ligand binding on the regulation of biomolecular condensates.
TL;DR: In this article, a review focused on describing the concepts of polyphasic linkage and the relevance of such a mechanism for controlling condensate formation and dissolution is presented. But, the authors focus on how ligand-mediated control over scaffold phase behavior can be quantified experimentally.
References
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Journal ArticleDOI
Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
TL;DR: Tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O–2 to O2 and H2O2 is reported.
Journal ArticleDOI
Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS
Mariely DeJesus-Hernandez,Ian R. A. Mackenzie,Bradley F. Boeve,Adam L. Boxer,Matt Baker,Nicola J. Rutherford,Alexandra M. Nicholson,Ni Cole A. Finch,Heather C. Flynn,Jennifer Adamson,Naomi Kouri,Aleksandra Wojtas,Pheth Sengdy,Ging-Yuek Robin Hsiung,Anna Karydas,William W. Seeley,Keith A. Josephs,Giovanni Coppola,Daniel H. Geschwind,Zbigniew K. Wszolek,Howard Feldman,Howard Feldman,David S. Knopman,Ronald C. Petersen,Bruce L. Miller,Dennis W. Dickson,Kevin B. Boylan,Neill R. Graff-Radford,Rosa Rademakers +28 more
TL;DR: It is found that repeat expansion in C9ORF72 is a major cause of both FTD and ALS, suggesting multiple disease mechanisms.
Journal ArticleDOI
TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
Jemeen Sreedharan,Ian P. Blair,Vineeta B. Tripathi,Xun Hu,Caroline Vance,Boris Rogelj,Steven Ackerley,Steven Ackerley,Jennifer C Durnall,Kelly L. Williams,Emanuele Buratti,Francisco E. Baralle,Jacqueline de Belleroche,J. Douglas Mitchell,P. Nigel Leigh,Ammar Al-Chalabi,Christopher C.J. Miller,Christopher C.J. Miller,Garth A. Nicholson,Garth A. Nicholson,Christopher Shaw +20 more
TL;DR: The evidence suggests a pathophysiological link between TDP-43 and ALS, and neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases.
Journal ArticleDOI
Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis.
Thomas J. Kwiatkowski,D. A. Bosco,D. A. Bosco,A. L. LeClerc,A. L. LeClerc,Eric Tamrazian,Charles R. Vanderburg,Carsten Russ,Carsten Russ,A. Davis,James M. Gilchrist,E. J. Kasarskis,Theodore L. Munsat,Paul N. Valdmanis,Guy A. Rouleau,Betsy A. Hosler,Pietro Cortelli,P. J. De Jong,Yuko Yoshinaga,Jonathan L. Haines,Margaret A. Pericak-Vance,Jianhua Yan,Nicola Ticozzi,Nicola Ticozzi,Nicola Ticozzi,Teepu Siddique,Diane McKenna-Yasek,Peter C. Sapp,Peter C. Sapp,H R Horvitz,John Landers,John Landers,Robert H. Brown,Robert H. Brown +33 more
TL;DR: Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders.
Journal ArticleDOI
Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6
Caroline Vance,Boris Rogelj,Tibor Hortobágyi,Kurt J. De Vos,Agnes L. Nishimura,Jemeen Sreedharan,Xun Hu,Bradley N. Smith,Deborah Ruddy,Paul Wright,Jeban Ganesalingam,Kelly L. Williams,Vineeta B. Tripathi,Safa Al-Saraj,Ammar Al-Chalabi,P. Nigel Leigh,Ian P. Blair,Garth A. Nicholson,Garth A. Nicholson,Jackie de Belleroche,Jean-Marc Gallo,Christopher C.J. Miller,Christopher C.J. Miller,Christopher Shaw +23 more
TL;DR: A missense mutation in the gene encoding fused in sarcoma (FUS) in a British kindred, linked to ALS6, is identified, which suggests that a common mechanism may underlie motor neuron degeneration.
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