What lava lamps and vinaigrette can teach us about cell biology

Dolgin, Elie

doi:10.1038/d41586-018-03070-2

Cited by 109 publications

(64 citation statements)

References 17 publications

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“…Phase separation has recently emerged as a new paradigm underlying the intracellular assembly of proteins and RNA with emergent collective material properties (thoroughly reviewed in Refs. [13][14][15][16]. Liquid-liquid phase separation, or the reversible process of a homogenous fluid de-mixing into two distinct liquid phases ( Fig.…”

Section: Phase Separation and Biomolecular Condensatesmentioning

confidence: 99%

“…new "phase" in cell biology (16) was pioneered with the demonstrated liquid-like properties of membraneless organelles, including the apparent wetting, fusion, and dynamic exchange of internal components of P granules, (germ granules native to Caenorhabditis elegans) (17), stress granules (18), and the nucleolus (19). In addition to membraneless organelles, various cellular functions, including signaling, cytoskeletal organization, and transcriptional regulation, have been shown to be accompanied by phase separation into condensed states with a range of material properties and are increasingly referred to as biomolecular condensates (15).…”

Section: Cro Reviewsmentioning

confidence: 99%

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Matter over mind: Liquid phase separation and neurodegeneration

Elbaum‐Garfinkle

2019

Journal of Biological Chemistry

200

157

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Phase separation of biomolecules leading to the formation of assemblies with distinct material properties has recently emerged as a new paradigm underlying subcellular organization. The discovery that disordered proteins, long associated with aggregation in neurodegenerative disease, are also implicated in driving liquid phase separation has galvanized significant interest in exploring the relationship between misregulated phase transitions and disease. This review summarizes recent work linking liquid phase separation to neurodegeneration, highlighting a pathological role for altered phase behavior and material properties of proteins assembled via liquid phase separation. The techniques that recent and current work in this area have deployed are also discussed, as is the potential for these discoveries to promote new research directions for investigating the molecular etiologies of neurodegenerative diseases.

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Section: Phase Separation and Biomolecular Condensatesmentioning

confidence: 99%

Section: Cro Reviewsmentioning

confidence: 99%

Matter over mind: Liquid phase separation and neurodegeneration

Elbaum‐Garfinkle

2019

Journal of Biological Chemistry

200

157

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“…It was argued that phase‐separated droplets of distinct chromatin states within the nucleus are mediated by class‐specific interactions of multivalent proteins, such as H3K27m3, H3K9m3, HP1α, and polycomb group proteins . In addition, phase separation may also help to concentrate certain molecules and exclude others creating diffusion barriers in the crowded environment of the IC . (Figure 2D)…”

Section: A Match Between the Anc‐inc Model And The Liquid Droplet Modmentioning

confidence: 99%

The Interchromatin Compartment Participates in the Structural and Functional Organization of the Cell Nucleus

et al. 2020

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This article focuses on the role of the interchromatin compartment (IC) in shaping nuclear landscapes. The IC is connected with nuclear pore complexes (NPCs) and harbors splicing speckles and nuclear bodies. It is postulated that the IC provides routes for imported transcription factors to target sites, for export routes of mRNA as ribonucleoproteins toward NPCs, as well as for the intranuclear passage of regulatory RNAs from sites of transcription to remote functional sites (IC hypothesis). IC channels are lined by less-compacted euchromatin, called the perichromatin region (PR). The PR and IC together form the active nuclear compartment (ANC). The ANC is co-aligned with the inactive nuclear compartment (INC), comprising more compacted heterochromatin. It is postulated that the INC is accessible for individual transcription factors, but inaccessible for larger macromolecular aggregates (limited accessibility hypothesis). This functional nuclear organization depends on still unexplored movements of genes and regulatory sequences between the two compartments.

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“…Also, liquid-liquid phase separation in cells may create enzyme-substrate droplets that greatly accelerate arginine methylation. [44] Fourth, the protein-protein interaction may introduce additional and enhanced binding for speedy transition of MMA to ADMA. In this regard, PRMTs have a general tendency to self- or cross-assemble into oligomeric architectures, [31a,37,45] a feature that can favorably increase local abundance of PRMTs to maximize their capacity to fully methylate their substrates.…”

Section: Processivity Of Arginine Methylationmentioning

confidence: 99%

Mechanisms and Inhibitors of Histone Arginine Methylation

Fulton

Brown

Zheng

2018

The Chemical Record

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Histone methylation plays an important regulatory role in chromatin restructuring and RNA transcription. Arginine methylation that is enzymatically catalyzed by the family of protein arginine methyltransferases (PRMTs) can either activate or repress gene expression depending on cellular contexts. Given the strong correlation of PRMTs with pathophysiology, great interest is seen in understanding molecular mechanisms of PRMTs in diseases and in developing potent PRMT inhibitors. Herein, we reviewed key research advances in the study of biochemical mechanisms of PRMT catalysis and their relevance to cell biology. We highlighted how a random binary, ordered ternary kinetic model for PRMT1 catalysis reconciles the literature reports and endorses a distributive mechanism that the enzyme active site utilizes for multiple turnovers of arginine methylation. We discussed the impacts of histone arginine methylation and its biochemical interplays with other key epigenetic marks. Challenges in developing small-molecule PRMT inhibitors were also discussed.

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What lava lamps and vinaigrette can teach us about cell biology

Cited by 109 publications

References 17 publications

Matter over mind: Liquid phase separation and neurodegeneration

Matter over mind: Liquid phase separation and neurodegeneration

The Interchromatin Compartment Participates in the Structural and Functional Organization of the Cell Nucleus

Mechanisms and Inhibitors of Histone Arginine Methylation

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