Phase separation on cell surface facilitates bFGF signal transduction with heparan sulphate

Xue, Song; Zhou, Fan; Zhao, Tian; Zhao, Huimin; Wang, Xuewei; Chen, Long; Li, Jinping; Luo, Shi-Zhong

doi:10.1038/s41467-022-28765-z

Cited by 43 publications

(19 citation statements)

References 41 publications

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“… 111 Xue et al. 135 recently reported basic fibroblast growth factors form condensates with heparan sulphate proteoglycans and activate FGFR signaling pathway. Besides, cytoplasmic scaffolds zonula occludens‐1, zonula occludens‐2, and claudins phase separate to regulate the assembly of tight junctions.…”

Section: Biological Functions Of Biomolecular Condensatesmentioning

confidence: 99%

Biomolecular condensates: Formation mechanisms, biological functions, and therapeutic targets

Niu

Zhang

et al. 2023

MedComm

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Biomolecular condensates are cellular structures composed of membraneless assemblies comprising proteins or nucleic acids. The formation of these condensates requires components to change from a state of solubility separation from the surrounding environment by undergoing phase transition and condensation. Over the past decade, it has become widely appreciated that biomolecular condensates are ubiquitous in eukaryotic cells and play a vital role in physiological and pathological processes. These condensates may provide promising targets for the clinic research. Recently, a series of pathological and physiological processes have been found associated with the dysfunction of condensates, and a range of targets and methods have been demonstrated to modulate the formation of these condensates. A more extensive description of biomolecular condensates is urgently needed for the development of novel therapies. In this review, we summarized the current understanding of biomolecular condensates and the molecular mechanisms of their formation. Moreover, we reviewed the functions of condensates and therapeutic targets for diseases. We further highlighted the available regulatory targets and methods, discussed the significance and challenges of targeting these condensates. Reviewing the latest developments in biomolecular condensate research could be essential in translating our current knowledge on the use of condensates for clinical therapeutic strategies.

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Section: Biological Functions Of Biomolecular Condensatesmentioning

confidence: 99%

Biomolecular condensates: Formation mechanisms, biological functions, and therapeutic targets

Niu

Zhang

et al. 2023

MedComm

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Section: Spla2s Are Globular Proteins But They Can Form Active Conden...mentioning

confidence: 99%

“…Two-dimensional condensates can also be formed on the membrane of the cell or internal organelles [ 70 ]. Recently, the formation of an extracellular condensate between fibroblast growth factor and HSPG has also been observed, which serves to enrich the growth factor around its receptor and trigger signaling transduction [ 70 ]. The same phenomenon can happen with the sPLA2s that interact with HSPGs on the cell surface, and activate an intracellular signal by yet unknown mechanisms, which also triggers their internalization.…”

Section: Spla2s Are Globular Proteins But They Can Form Active Conden...mentioning

confidence: 99%

Secretory Phospholipases A2, from Snakebite Envenoming to a Myriad of Inflammation Associated Human Diseases—What Is the Secret of Their Activity?

Tonello

2023

IJMS

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Secreted phospholipases of type A2 (sPLA2s) are proteins of 14–16 kDa present in mammals in different forms and at different body sites. They are involved in lipid transformation processes, and consequently in various immune, inflammatory, and metabolic processes. sPLA2s are also major components of snake venoms, endowed with various toxic and pharmacological properties. The activity of sPLA2s is not limited to the enzymatic one but, through interaction with different types of molecules, they exert other activities that are still little known and explored, both outside and inside the cells, as they can be endocytosed. The aim of this review is to analyze three features of sPLA2s, yet under-explored, knowledge of which could be crucial to understanding the activity of these proteins. The first feature is their disulphide bridge pattern, which has always been considered immutable and necessary for their stability, but which might instead be modulable. The second characteristic is their ability to undergo various post-translational modifications that would control their interaction with other molecules. The third feature is their ability to participate in active molecular condensates both on the surface and within the cell. Finally, the implications of these features in the design of anti-inflammatory drugs are discussed.

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“…This limits the prospect of LLPS in drug development. Our recent work demonstrated that cytokines like bFGF could undergo LLPS on cell surface with its receptor, which plays important role for effective signal transduction 4 . Inspired by the discovery, we realized that condensing functioning molecules on speci c cells was possible by utilizing LLPS, which can be developed as a powerful biological tool for targeted delivery of massive number of molecules.…”

Section: Introductionmentioning

confidence: 99%

Phase separation enhanced drug delivery system for anti-cancer therapy

Bai

Pei

Duan

et al. 2022

Preprint

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The cellular phase-separated condensates compartmentalize and concentrate biomolecules with distinct physicochemical properties, which has great potential for therapy purposes. However, the discovered phase separation phenomena in living organisms were restricted intracellularly, which limits the biomedical application of phase separation. Here, we designed a phase separation enhanced delivery system to specifically condensate molecules on the cell surface for efficient drug delivery. As a proof of concept, we demonstrated that an anti-cancer drug conjugate can selectively co-phase separate with the targeting component on cancer cell surface and efficiently kill the cells after internalization. Both cellular and in vivo assays showed more potency with this system than traditional antibody conjugates. The method provides insights in the application of phase separation as a powerful tool for therapeutic purpose.

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Phase separation on cell surface facilitates bFGF signal transduction with heparan sulphate

Cited by 43 publications

References 41 publications

Biomolecular condensates: Formation mechanisms, biological functions, and therapeutic targets

Biomolecular condensates: Formation mechanisms, biological functions, and therapeutic targets

Secretory Phospholipases A2, from Snakebite Envenoming to a Myriad of Inflammation Associated Human Diseases—What Is the Secret of Their Activity?

Phase separation enhanced drug delivery system for anti-cancer therapy

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