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

Phase separation on cell surface facilitates bFGF signal transduction with heparan sulphate.
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细胞表面的相分离促进 bFGF 与硫酸乙酰肝素的信号转导

DOI:
10.1038/s41467-022-28765-z
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发表时间:
2022-03-02
影响因子:
16.6
通讯作者:
Luo SZ
Luo SZ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Xue S;Zhou F;Zhao T;Zhao H;Wang X;Chen L;Li JP;Luo SZ

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液-液相分离(LLPS)在多种细胞过程中发挥着重要作用,包括无膜细胞器的构建、染色质浓缩、内膜信号转导等。目前的看法是LLPS依赖于弱的多价相互作用和细胞内拥挤的环境。在这项研究中,我们证明硫酸乙酰肝素可以作为一个平台,诱导细胞表面的碱性成纤维细胞生长因子的相分离。相分离模型提供了bFGF如何富集到其受体的替代机制,从而触发信号转导。该研究提供了硫酸乙酰肝素如何将生长因子募集到细胞表面并执行其功能的机制,扩展了人们对细胞水平上从细胞内到细胞外蛋白质相分离的看法。据报道,液-液相分离(LLPS)发生在细胞内环境中。在这里,作者表明硫酸乙酰肝素作为碱性成纤维细胞生长因子在细胞表面进行LLPS的平台,因此促进下游信号传导。
Liquid-liquid phase separation (LLPS) plays important roles in various cellular processes, facilitating membrane-less organelles construction, chromatin condensation, signal transduction on inner membrane and many other processes. Current perception is that LLPS relies on weak multivalent interactions and crowded environments intracellularly. In this study, we demonstrate that heparan sulfate can serve as a platform to induce the phase separation of basic fibroblast growth factor on cell surface. The phase separation model provides an alternative mechanism how bFGF is enriched to its receptors, therefore triggering the signaling transduction. The research provides insights on the mechanism how growth factors can be recruited to cell surface by heparan sulfate and execute their functions, extending people’s view on phase separation from intracellular to extracellular proteins at cellular level. Liquid-liquid phase separation (LLPS) is reported to occur in the intracellular environment. Here the authors show that heparan sulphate serves as a platform for basic fibroblast growth factor to undergo LLPS on the cell surface, therefore facilitating downstream signalling
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