Drops and fibers — how biomolecular condensates and cytoskeletal filaments influence each other

Wiegand, Tina; Hyman, Anthony

doi:10.1042/etls20190174

Cited by 71 publications

(68 citation statements)

References 119 publications

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“…Both functions involve using condensates to alter the concentrations of reactants and thus the rates or timing of reactions. A very different set of proposed functions involves the ability of condensates to resist mechanical force (38) or even generate it (63).…”

Section: Functions Of Established Biomolecular Condensatesmentioning

confidence: 99%

“…or even generate it(63).Though sometime left of our discussions of condensate function, is not surprising that assembly of condensates (which could be considered a type of 3D polymerization) would be able to generate mechanical force, given the well-demonstrated ability of actin and tubulin polymerization to generate force(64,65). Finally, another set of proposed functions for condensates, one which overlaps with the ideas above, is that they play a role in signal transduction(66).…”

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confidence: 92%

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Overexpression of the microtubule-binding protein CLIP-170 induces a +TIP network superstructure consistent with a biomolecular condensate

Bryant

Nelson

et al. 2021

Preprint

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Proper regulation of microtubule (MT) dynamics is critical for cellular processes including cell division and intracellular transport. Plus-end tracking proteins (+TIPs) dynamically track growing MTs and play a key role in MT regulation. +TIPs participate in a complex web of intra- and inter-molecular interactions known as the +TIP network. Hypotheses addressing the purpose of +TIP:+TIP interactions include relieving +TIP autoinhibition and localizing MT regulators to growing MT ends. In addition, we have proposed that the web of +TIP:+TIP interactions has a physical purpose, creating a superstructure that constrains the structural fluctuations of the fragile MT tip and thus acts as a polymerization chaperone. Many animal +TIP network proteins are multivalent and have intrinsically disordered regions, features commonly found in biomolecular condensates. This observation suggests that the +TIP network might under some conditions form a biomolecular condensate. Previous studies have shown that overexpression of the +TIP CLIP-170 induces large “patch” structures containing CLIP-170 and other +TIPs. To test the hypothesis that these patches might be biomolecular condensates, we used video microscopy, immunofluorescence staining, and Fluorescence Recovery After Photobleaching (FRAP). Our data show that the CLIP-170-induced patches have hallmarks indicative of a biomolecular condensate, one that contains +TIP proteins and excludes other known condensate markers. Moreover, bioinformatic studies demonstrate that the presence of intrinsically disordered regions is conserved in key +TIPs, implying that these regions are functionally significant. Together, these results indicate that the CLIP-170 induced patches in cells are phase-separated liquid condensates and raise the possibility that the endogenous +TIP network might form a liquid droplet at MT ends or other +TIP locations.

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Section: Functions Of Established Biomolecular Condensatesmentioning

confidence: 99%

mentioning

confidence: 92%

Overexpression of the microtubule-binding protein CLIP-170 induces a +TIP network superstructure consistent with a biomolecular condensate

Bryant

Nelson

et al. 2021

Preprint

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“…Accumulating data indicate that cellular condensates are spatially regulated and can interact with other subcellular structures and compartments 1,40 . To test whether our designer condensates would be amenable to such specific subcellular localization, we fused the PopTag to different “cellular anchors” - tethering the condensates in the plasma membrane, on microtubules, or on the surface of lipid droplets (Fig.…”

Section: Introductionmentioning

confidence: 99%

A modular platform for engineering function of natural and synthetic biomolecular condensates

Lasker

Boeynaems

et al. 2021

Preprint

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Phase separation is emerging as a universal principle for how cells use dynamic subcompartmentalization to organize biochemical reactions in time and space. Yet, whether the emergent physical properties of these biomolecular condensates are important for their biological function remains unclear. The intrinsically disordered protein PopZ forms membraneless condensates at the poles of the bacterium Caulobacter crescentus and selectively sequesters kinase-signaling cascades to regulate asymmetric cell division. By dissecting the molecular grammar underlying PopZ phase separation, we find that unlike many eukaryotic examples, where unstructured regions drive condensation, a structured domain of PopZ drives condensation, while conserved repulsive features of the disordered region modulate material properties. By generating rationally designed PopZ mutants, we find that the exact material properties of PopZ condensates directly determine cellular fitness, providing direct evidence for the physiological importance of the emergent properties of biomolecular condensates. Our work codifies a clear set of design principles illuminating how sequence variation in a disordered domain alters the function of a widely conserved bacterial condensate. We used these insights to repurpose PopZ as a modular platform for generating synthetic condensates of tunable function in human cells.

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“…A growing number of examples illustrate the importance of biophysical interactions between condensates and the cytoskeleton. While cytoskeletal fibers can act as platforms that promote condensation by increasing local concentrations (Hernandez-Vega et al, 2017; Wiegand and Hyman, 2020), viscoelastic fibers can restrict condensate dynamics and fusion. Such cytoskeleton-driven spatial segregation of condensates has been observed in the Xenopus laevis oocyte nucleus, where a nuclear actin network prevents sinking and fusion of nucleoli, and also recently documented keratinocytes (Feric and Brangwynne, 2013; Quiroz et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Liquid-to-solid phase transition ofoskarRNP granules is essential for their function in theDrosophilagermline

Bose

Mahamid²,

Ephrussi

2021

Preprint

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Asymmetric localization of oskar RNP granules to the oocyte posterior is crucial for abdominal patterning and germline formation of the Drosophila embryo. We show that oskar RNP granules in the oocyte are condensates with solid-like physical properties. Using purified oskar RNA and scaffold proteins Bruno and Hrp48, we confirm in vitro that oskar granules undergo a liquid-to-solid phase transition. Whereas the liquid phase allows RNA incorporation, the solid phase precludes incorporation of additional RNA while allowing RNA-dependent partitioning of specific proteins. Genetic modification of scaffold granule proteins, or tethering the intrinsically disordered region of human Fused in Sarcoma to oskar mRNA, allowed modulation of granule material properties in vivo. The resulting liquid-like properties impaired oskar localization and translation with severe consequences on embryonic development. Our study reflects how physiological phase transitions shape RNA-protein condensates to regulate localization and expression of a maternal RNA that instructs germline formation.

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Drops and fibers — how biomolecular condensates and cytoskeletal filaments influence each other

Cited by 71 publications

References 119 publications

Overexpression of the microtubule-binding protein CLIP-170 induces a +TIP network superstructure consistent with a biomolecular condensate

Overexpression of the microtubule-binding protein CLIP-170 induces a +TIP network superstructure consistent with a biomolecular condensate

A modular platform for engineering function of natural and synthetic biomolecular condensates

Liquid-to-solid phase transition ofoskarRNP granules is essential for their function in theDrosophilagermline

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