Regulation of Transmembrane Signaling by Phase Separation

Case, Lindsay B.; Ditlev, Jonathon A.; Rosen, Michael K.

doi:10.1146/annurev-biophys-052118-115534

Cited by 254 publications

(235 citation statements)

References 183 publications

(225 reference statements)

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“…In recent years, phase separation has garnered much attention as a mechanism for assembly of many cellular structures, including signalling clusters of membrane receptors (Case et al, 2019a). Liquid, phase-separated biomolecular condensates also form many cellular organelles which are not bound by membranes, such as P-granules, nucleoi, stress granules and others (Banani et al, 2017;Shin and Brangwynne, 2017).…”

Section: Introductionmentioning

confidence: 99%

Phase separation of Ede1 promotes the initiation of endocytic events

Kozak

Kaksonen

2019

Preprint

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Clathrin-mediated endocytosis is a major pathway that eukaryotic cells use to produce transport vesicles from the plasma membrane. The assembly of the endocytic coat is initiated by a dynamic network of weakly interacting proteins, but the exact mechanism of initiation is unknown. Ede1, the yeast homologue of mammalian Eps15, is one of the early-arriving endocytic proteins and a key initiation factor. In the absence of Ede1, most other early endocytic proteins lose their punctate localization and the frequency of endocytic initiation is decreased. We show here that in mutants with increased amounts of cytoplasmic Ede1, the excess protein forms large condensates which exhibit properties of phase separated liquid protein droplets. These Ede1 condensates recruit many other early-arriving endocytic proteins. Their formation depends on the core region of Ede1 that contains a coiled coil and a low-complexity domain. We demonstrate that Ede1 core region is essential for the endocytic function of Ede1. The core region can also promote clustering of a heterologous lipid-binding domain into discrete sites on the plasma membrane that initiate endocytic events. We propose that the clustering of the early endocytic proteins and cargo depend on phase separation mediated by Ede1.

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Section: Introductionmentioning

confidence: 99%

Phase separation of Ede1 promotes the initiation of endocytic events

Kozak

Kaksonen

2019

Preprint

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“…Similarly, various protein modifications have been shown to modulate condensate assembly (reviewed in Reference ), composition (reviewed in Reference ) and material properties . Second, association to nearby structures, such as membranes, can also promote condensate assembly (eg, actin or Ras signaling cluster assembly).…”

Section: Biomolecular Condensates: Assembly Function and Regulationmentioning

confidence: 99%

Biomolecular condensates in neurodegeneration and cancer

Spannl

Tereshchenko

Mastromarco

et al. 2019

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The intracellular environment is partitioned into functionally distinct compartments containing specific sets of molecules and reactions. Biomolecular condensates, also referred to as membrane‐less organelles, are diverse and abundant cellular compartments that lack membranous enclosures. Molecules assemble into condensates by phase separation; multivalent weak interactions drive molecules to separate from their surroundings and concentrate in discrete locations. Biomolecular condensates exist in all eukaryotes and in some prokaryotes, and participate in various essential house‐keeping, stress‐response and cell type‐specific processes. An increasing number of recent studies link abnormal condensate formation, composition and material properties to a number of disease states. In this review, we discuss current knowledge and models describing the regulation of condensates and how they become dysregulated in neurodegeneration and cancer. Further research on the regulation of biomolecular phase separation will help us to better understand their role in cell physiology and disease.

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“…

Membranes orchestrate cellular life. In addition to compartmentalizing the cell into organelles, membranes can organize their embedded proteins into specialized domains, concentrating molecular partners together to drive biological processes (1,2). Due to the labile and often transient nature of these membrane domains, it remains a challenge to study how individual protein complexes are organized within them.The question of membrane domain organization is especially pertinent to thylakoids, sheet-like membrane-bound compartments that produce oxygen while converting light energy into biochemical energy, thereby sustaining most of the life on Earth.

…”

mentioning

confidence: 99%

“…Membranes orchestrate cellular life. In addition to compartmentalizing the cell into organelles, membranes can organize their embedded proteins into specialized domains, concentrating molecular partners together to drive biological processes (1,2). Due to the labile and often transient nature of these membrane domains, it remains a challenge to study how individual protein complexes are organized within them.…”

mentioning

confidence: 99%

Charting the native architecture of thylakoid membranes with single-molecule precision

Wietrzyñski

Schaffer

Tegunov

et al. 2019

Preprint

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Thylakoid membranes scaffold an assortment of large protein complexes that work together to harness the energy of light to produce oxygen, NADPH, and ATP. It has been a longstanding challenge to visualize how the intricate thylakoid network organizes these protein complexes to finely tune the photosynthetic reactions. Using cryo-electron tomography to analyze membrane surface topology, we have mapped the native molecular landscape of thylakoid membranes within green algae cells. Our tomograms provide insights into the molecular forces that drive thylakoid stacking and reveal that photosystems I and II are strictly segregated at the borders between appressed and non-appressed membrane domains. This new approach to charting thylakoid topology lays the foundation for dissecting photosynthetic regulation at the level of single protein complexes within the cell.

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Regulation of Transmembrane Signaling by Phase Separation

Cited by 254 publications

References 183 publications

Phase separation of Ede1 promotes the initiation of endocytic events

Phase separation of Ede1 promotes the initiation of endocytic events

Biomolecular condensates in neurodegeneration and cancer

Charting the native architecture of thylakoid membranes with single-molecule precision

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