Van Laethem F, Leo O
Laboratoire de Physiologie Animale, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium.
Curr Mol Med. 2002 Sep;2(6):557-70. doi: 10.2174/1566524023362122.
Engagement of immune receptors by antigen may lead to activation, cell proliferation, differentiation and effector functions. It has recently been proposed that the initiation and propagation of the signaling events taking place in immune cells occur in specialized membrane regions called lipid rafts. These detergent-insoluble glycolipid domains are specialized membrane compartments enriched in cholesterol and glycolipids. They also contain many lipid-modified signaling proteins such as tyrosine kinases of the Src family, GPI (glycosylphosphatidylinositol)-linked proteins as well as adaptor proteins. The confinement of signaling molecules in membrane subdomains suggests that lipid rafts function as platforms for the formation of multicomponent transduction complexes. Indeed, upon receptor binding, immune receptors become raft-associated and additional components of the signaling pathways are recruited to rafts in order to form signaling complexes. It has been speculated that the entry of immune receptors into rafts can regulate cell activation. Accordingly, numerous experiments have provided substantial evidence that raft integrity is crucial for the initiation and maintenance of intracellular signals. Recent studies have also shown that the access and translocation of immune receptors to lipid rafts are developmentally regulated (immature versus mature cells, Th1 versus Th2 lymphocytes) and sensitive to pharmacological agents. The aim of the present review is to summarize the current knowledge of immune receptor signal transduction with particular emphasis on the role of membrane compartments in immune activation. Finally, experimental evidences indicating that these membrane structures may represent clinically relevant potential targets for immune regulation, will be discussed.
抗原与免疫受体的结合可能导致激活、细胞增殖、分化及效应功能。最近有人提出，免疫细胞中发生的信号事件的起始和传播发生在称为脂筏的特殊膜区域。这些不溶于去污剂的糖脂结构域是富含胆固醇和糖脂的特殊膜区室。它们还包含许多脂质修饰的信号蛋白，如Src家族的酪氨酸激酶、糖基磷脂酰肌醇（GPI）连接蛋白以及衔接蛋白。信号分子在膜亚结构域中的聚集表明脂筏作为多组分转导复合物形成的平台发挥作用。事实上，在受体结合后，免疫受体与脂筏相关联，信号通路的其他组分被招募到脂筏中以形成信号复合物。据推测，免疫受体进入脂筏可调节细胞激活。因此，大量实验提供了充分证据表明脂筏完整性对于细胞内信号的起始和维持至关重要。最近的研究还表明，免疫受体进入和转运到脂筏受到发育调控（未成熟细胞与成熟细胞、Th1细胞与Th2淋巴细胞），并且对药物敏感。本综述的目的是总结免疫受体信号转导的当前知识，特别强调膜区室在免疫激活中的作用。最后，将讨论表明这些膜结构可能代表免疫调节临床相关潜在靶点的实验证据。
