Phase separation and viral factories: unveiling the physical processes supporting RNA packaging in dsRNA viruses DOI Creative Commons
Christina Haller, Julia Acker, A. Emilia Arguello

et al.

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 26, 2024

Understanding of the physicochemical properties and functions biomolecular condensates has rapidly advanced over past decade. More recently, many RNA viruses have been shown to form cytoplasmic replication factories, or viroplasms, via phase separation their components, akin numerous cellular membraneless organelles. Notably, diverse from Reoviridae family containing 10–12 segmented double-stranded genomes induce formation viroplasms in infected cells. Little is known about inner workings these inclusions how they may support stoichiometric assembly with genomes, raising questions roles coordinating viral genome packaging. Here, we discuss molecular composition determines properties, highlighting interplay between structure, remodelling, condensate self-organisation. Advancements structural probing theoretical modelling can reveal mechanisms through which ribonucleoprotein complexes selective enrichment distinct RNAs.

Language: Английский

Microscopic and stochastic simulations of chemically active droplets DOI
Roxanne Berthin,

Jacques Fries,

Marie Jardat

et al.

Physical review. E, Journal Year: 2025, Volume and Issue: 111(2)

Published: Feb. 24, 2025

Biomolecular condensates play a central role in the spatial organization of living matter. Their formation is now well understood as form liquid-liquid phase separation that occurs very far from equilibrium. For instance, they can be modeled active droplets, where combination molecular interactions and chemical reactions result microphase separation. However, so far, models chemically droplets are spatially continuous deterministic. Therefore, relationship between microscopic parameters some crucial properties (such their polydispersity, shape anisotropy, or typical lifetime) yet to established. In this work, we address question computationally, using Brownian dynamics simulations droplets: building blocks represented explicitly particles interact with attractive repulsive interactions, depending on whether droplet-forming state not. Thanks stochastic view problem, reveal how driving system away equilibrium controlled way determines fluctuations emulsions.

Language: Английский

Citations

0
Dynamic structure of the cytoplasm DOI Creative Commons
Hyo-Jun Kim, Morgan Delarue

Current Opinion in Cell Biology, Journal Year: 2025, Volume and Issue: 94, P. 102507 - 102507

Published: April 6, 2025

The cytoplasm is a dense and complex milieu in which plethora of biochemical reactions occur. Its structure not understood so far, albeit being central to cellular functioning. In this review, we highlight novel perspective the physical properties are regulated space time actively contribute function. Furthermore, underscore recent findings that dynamic formation local assemblies within cytoplasm, such as condensates polysomes, serves key regulator mesoscale cytoplasmic dynamics.

Language: Английский

Citations

0
Multiphasic protein condensation governed by shape and valency DOI Creative Commons
Vikas Pandey, Tomohisa Hosokawa, Yasunori Hayashi

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 115504 - 115504

Published: April 1, 2025

Language: Английский

Citations

0
Molecular Matchmakers: How ATP and Small Amphiphilic Molecules Fine-Tune FET Proteins Clusters DOI
Mrityunjoy Kar

Published: April 16, 2025

Abstract FET (FUS-EWSR1-TAF15) family proteins inherently form mesoscale molecular assemblies, known as clusters, under physiological conditions at concentrations well below the threshold for phase separation. This study demonstrates that adenosine triphosphate (ATP), an amphiphilic molecule and essential cellular metabolite, modulates size of these sub-saturation clusters in a concentration-dependent manner. At low (1-2 mM), ATP acts crosslinker proteins, resulting larger clusters. moderate (5 decreases but stabilizes. high (10 cluster further diminishes. Other molecules, including common hydrotropes like sodium xylene sulfonate, toluene hexanediol, exhibit comparable effects on protein clustering. Notably, cannot be explained solely by hydrotropic or kosmotropic mechanisms; instead, they stem from non-specific interactions between small molecules. The intrinsic chemical properties molecules play crucial role regulating formation concentrations.

Language: Английский

Citations

0
Mesoscale condensates organize the cytoplasm DOI

Leshani Ahangama Liyanage,

Jonathon A. Ditlev

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(3), P. 310 - 312

Published: Feb. 29, 2024

Language: Английский

Citations

2
Disease-linked mutations dysregulate neuronal condensate physical properties, composition, and RNA translation DOI Creative Commons

Leshani Ahangama Liyanage,

Fraser P. McCready,

Steve Chung

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 3, 2024

Abstract Local RNA translation is essential for development. In neurons, deficient local linked with mutations in scaffold proteins results dysregulated dendrite and dendritic spine growth. However, mechanisms by which these control how disease-linked induce aberrant were unclear. We use biochemical reconstitution neuronal assays to show that the condensate shank2 cause physical hardening altered composition of condensates; a key translation-modulator FMRP excluded from mutant condensates. Functionally, condensates repress while composed intrinsically disordered region-localized missense promote translation. These demonstrate dysregulation properties an underlying mechanism often observed disease. One Sentence Summary Disease-linked postsynaptic density protein dysregulate phase separated biomolecular resulting

Language: Английский

Citations

2
The potential role of liquid–liquid phase separation in the cellular fate of the compartments for unconventional protein secretion DOI
Luís F.S. Mendes,

Carolina O. Gimenes,

Marília D. O. da Silva

et al.

Protein Science, Journal Year: 2024, Volume and Issue: 33(7)

Published: June 26, 2024

Abstract Eukaryotic cells have developed intricate mechanisms for biomolecule transport, particularly in stressful conditions. This interdisciplinary study delves into unconventional protein secretion (UPS) pathways activated during starvation, facilitating the export of proteins bypassing most components classical secretory machinery. Specifically, we focus on underexplored GRASP's role UPS, biogenesis and cargo recruitment vesicular‐like compartment UPS. Our results show that liquid–liquid phase separation (LLPS) plays a key coacervation Grh1, GRASP yeast homologue, under starvation‐like association seems precursor to Compartment Unconventional Protein Secretion (CUPS) biogenesis. Grh1's self‐association is regulated by electrostatic, hydrophobic, hydrogen‐bonding interactions. Importantly, our demonstrates phase‐separated states Grh1 can recruit UPS situations. Additionally, explore how coacervate liquid‐to‐solid transition could impact cells' ability return normal post‐stress states. findings offer insights intracellular dynamics cell adaptive responses stress.

Language: Английский

Citations

2
Exploring the role of macromolecular crowding and TNFR1 in cell volume control DOI Creative Commons
Parijat Biswas, Priyanka Roy, Subhamoy Jana

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Sept. 19, 2024

The excessive cosolute densities in the intracellular fluid create a physicochemical condition called macromolecular crowding (MMC). Intracellular MMC entropically maintains biochemical thermodynamic equilibria by favoring associative reactions while hindering transport processes. Rapid cell volume shrinkage during extracellular hypertonicity elevates and disrupts equilibria, potentially ushering death. Consequently, cells actively counter hypertonic stress through regulatory increase (RVI) restore homeostasis. Here, we establish fluorescence anisotropy of EGFP as reliable tool for studying cellular explore spatiotemporal dynamics instabilities under multiple conditions. Our studies reveal that actin cytoskeleton enforces spatially varying levels inside adhered cells. Within populations, is uncorrelated with nuclear DNA content but anti-correlated spread area. Although different lines have statistically similar distributions, their responses to vary. intensity determines cell’s ability RVI, which correlates factor kappa beta (NFkB) activation. Pharmacological inhibition knockdown experiments tumor necrosis receptor 1 (TNFR1) initiates hypertonicity-induced NFkB signaling RVI. At severe hypertonicities, elevated amplifies cytoplasmic microviscosity hinders interacting protein kinase (RIPK1) recruitment at TNFR1 complex, incapacitating TNFR1-NFkB consequently, Together, our unveil involvement modulating RVI demonstrate pivotal role determining osmoadaptability.

Language: Английский

Citations

2
Condensation of the β‐cell secretory granule luminal cargoes pro/insulin and ICA512 RESP18 homology domain DOI Creative Commons

Pamela L. Toledo,

Diego S. Vazquez,

Alejo R. Gianotti

et al.

Protein Science, Journal Year: 2023, Volume and Issue: 32(6)

Published: May 10, 2023

Abstract ICA512/PTPRN is a receptor tyrosine‐like phosphatase implicated in the biogenesis and turnover of insulin secretory granules (SGs) pancreatic islet beta cells. Previously we found biophysical evidence that its luminal RESP18 homology domain (RESP18HD) forms biomolecular condensate interacts with vitro at close‐to‐neutral pH, is, conditions resembling those present early pathway. Here provide further for relevance these findings by showing pH 6.8 RESP18HD also proinsulin—the physiological precursor pathway major cargo β‐cell nascent SGs. Our light scattering analyses indicate proinsulin, but insulin, populate nanocondensates ranging size from 15 to 300 nm 10e2 10e6 molecules. Co‐condensation proinsulin/insulin transforms initial into microcondensates (size >1 μm). The intrinsic tendency proinsulin self‐condensate implies that, ER, chaperoning mechanism must arrest spontaneous intermolecular condensation allow proper intramolecular folding. These data suggest an driver SG biogenesis, process which co‐condensation participates their phase separation other proteins transit through same compartments destined routes. Through cytosolic tail ICA512, may orchestrate recruitment factors involved membrane budding fission transport vesicles

Language: Английский

Citations

6
Protein nanocondensates: the next frontier DOI

Pamela L. Toledo,

Alejo R. Gianotti,

Diego S. Vazquez

et al.

Biophysical Reviews, Journal Year: 2023, Volume and Issue: 15(4), P. 515 - 530

Published: Aug. 1, 2023

Language: Английский

Citations

5