Last, we show that translation of FMRP-bound RNAs is reduced in vivo in FUS-ALS motor neurons. This leads to repression of translation in mouse and human FUS-ALS motor neurons and is corroborated in vitro, where FUS and FMRP copartition and repress translation. We show that in axons, mutant FUS condensates sequester and promote the phase separation of fragile X mental retardation protein (FMRP), another RBP associated with neurodegeneration. Here, we use mouse and human models with endogenous ALS-associated mutations to study the early consequences of increased cytoplasmic FUS. FUS mutations lead to its cytoplasmic mislocalization and cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Forman-Kay, Giampietro Schiavo, and Pietro Fratta Show FewerįUsed in Sarcoma (FUS) is a multifunctional RNA binding protein (RBP). Fisher, Alessandro Rosa, Gabriella Viero, Julie D. Nosella, Anny Devoy, Cristian Bodo, Rafaela Fernandez de la Fuente, Elizabeth M. Andrew Chong, Jack Humphrey, … Show All …, Seth Jarvis, Melis Pisiren, Oscar G. Ule, Maria Giovanna Garone, Brian Tsang, Francesca Mattedi, P. Read more about how to correctly acknowledge RSC content.Nicol Birsa, Agnieszka M. Permission is not required) please go to the Copyright If you want to reproduce the wholeĪrticle in a third-party commercial publication (excluding your thesis/dissertation for which If you are the author of this article, you do not need to request permission to reproduce figuresĪnd diagrams provided correct acknowledgement is given. Provided correct acknowledgement is given. If you are an author contributing to an RSC publication, you do not need to request permission Please go to the Copyright Clearance Center request page. To request permission to reproduce material from this article in a commercial publication, Provided that the correct acknowledgement is given and it is not used for commercial purposes. This article in other publications, without requesting further permission from the RSC, Interplay between intrinsically disordered proteins inside membraneless protein liquid dropletsĬreative Commons Attribution-NonCommercial 3.0 Unported Licence. ![]() The present study not only reports multiple peculiar behaviors of interacting IDP pairs inside droplets but also provides valuable information on generating membraneless organelle models with controllable droplet properties. Interestingly, some droplets were heterogeneously fused with segregated subcompartments, and this segregation was enhanced by droplet maturation and was more apparent for specific IDP pairs, in which the polar and charged residue compositions are highly different. We also discovered that droplets of different IDPs could rapidly fuse to each other. Among the five tested IDPs, the disordered region of Ddx4 helicase with its unique multiple charged residue blocks was noticeably influenced by droplet mobility. The recruited IDPs were mostly mobile even inside highly immobile droplets. Three different IDP droplets actively recruited other diverse IDPs inside droplets with extremely varied enrichment (inside/outside) degrees (over 100-fold variation) under highly crowded conditions. Here, we develop a rapid IDP clustering system to generate protein droplets with varied residue compositions and examine diverse interacting IDPs inside droplets. However, how potential interactions between different IDPs affect the dynamic behavior of these protein droplets is largely unknown. Intrinsically disordered proteins (IDPs) in cells phase separate to form diverse membraneless organelles, which have condensed liquid droplet-like properties and often contain multiple IDPs.
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