Intracellular lipid flux and membrane microdomains as organizing principles in inflammatory cell signaling.
Intracellular lipid flux and membrane microdomains as organizing principles in inflammatory cell signaling.
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DOI：
10.4049/jimmunol.1100253
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发表时间：
2011-08-15
期刊：
影响因子：
--
通讯作者：
Parks JS
中科院分区：
文献类型：
--
作者：
Fessler MB;Parks JS
脂筏和小窝在Toll样受体（TLR）4和其他几种免疫受体的信号组织中起着关键作用。除了这些膜微结构域划分的信号事件的简单编目，最近的研究已经揭示了膜脂质结构域的动态重塑对免疫信号传导的惊人的核心重要性。对膜脂质的简单干预，如胆固醇负载或筏脂质交联的变化，足以诱导膜及其蛋白质货物的微米级重排，随之而来的信号转导。在这篇综述中，使用TLR信号在巨噬细胞作为一个中心焦点，我们讨论了新出现的证据表明，环境和遗传扰动的膜脂质调节蛋白质信号，说明如何稳态流动的胆固醇和其他脂质通过筏调节先天性免疫反应，并强调最近的尝试利用这些见解对治疗的发展。
Lipid rafts and caveolae play a pivotal role in organization of signaling by Toll-like Receptor (TLR)4 and several other immune receptors. Beyond the simple cataloguing of signaling events compartmentalized by these membrane microdomains, recent studies have revealed the surprisingly central importance of dynamic remodeling of membrane lipid domains to immune signaling. Simple interventions upon membrane lipid, such as changes in cholesterol loading or crosslinking of raft lipids, are sufficient to induce micron-scale reordering of membranes and their protein cargo with consequent signal transduction. In this review, using TLR signaling in the macrophage as a central focus, we discuss emerging evidence that environmental and genetic perturbations of membrane lipid regulate protein signaling, illustrate how homeostatic flow of cholesterol and other lipids through rafts regulates the innate immune response, and highlight recent attempts to harness these insights towards therapeutic development.
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