Intracellular signaling in M-CSF-induced microglia activation: Role of Iba1
Intracellular signaling in M-CSF-induced microglia activation: Role of Iba1
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DOI：
10.1002/glia.10149
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发表时间：
2002-11-01
期刊：
影响因子：
6.2
通讯作者：
Kohsaka, S
中科院分区：
文献类型：
--
作者：
Imai, Y;Kohsaka, S
小胶质细胞被脑损伤或疾病引起的各种环境刺激反应性激活。活化的小胶质细胞表现出形态转化、增殖、迁移、吞噬作用和生物活性分子的产生。各种分子被报道和建议激活小胶质细胞。其中，巨噬细胞集落刺激因子（macrophage-colony-stimulating factor，M-CSF）被认为是维持小胶质细胞活化特性的最有说服力的候选者之一。因此，本研究的重点是在细胞内分子事件产生的下游M-CSF刺激。M-CSF激活其受体Fins酪氨酸激酶，Fins依次激活许多信号分子，包括PI 3 K或磷脂酶C γ（PLC γ）。刺激持续的信号级联导致小GT3，Rac，小胶质细胞活化中的关键分子的活化。已知Rac在受体酪氨酸激酶的下游被激活，并调节肌动蛋白细胞骨架的重组，这深刻地奠定了激活的小胶质细胞的上述性质。Iba 1是一种巨噬细胞/小胶质细胞特异性钙结合蛋白，被我们的研究小组鉴定，并被证明参与Rac信号通路。此外，我们引入了一种新的信号通路，其中Rac被激活，依赖于PLC γ和Iba 1。然而，要了解小胶质细胞激活的分子细节，还需要进一步的工作。(C)2002 Wiley-Liss，Inc.
Microglia are reactively activated by various environmental stimulations caused by brain injury or disease. Activated microglia exhibit morphological transformation, proliferation, migration, phagocytosis, and the production of bioactive molecules. Various molecules are reported and suggested to activate microglia. Among them, macrophage-colony-stimulating factor (M-CSF) is considered one of the most convincing candidates responsible for maintaining activation properties of microglia. Therefore, the focus of the present study is on intracellular molecular events that arise downstream of M-CSF stimulation. M-CSF activates its receptor, Fins tyrosine kinase, and Fins sequentially activates a number of signaling molecules, including PI3K or phospholipase Cgamma (PLCgamma). Stimulation of continuing signaling cascades results in the activation of a small GTPase, Rac, the key molecule in microglia activation. Rac is known to be activated downstream of receptor tyrosine kinases and to regulate reorganization of the actin cytoskeleton, which profoundly underlies the above-mentioned properties of activated microglia. Iba1, a macrophage/microglia-specific calcium-binding protein, was identified by our group and was shown to be involved in the Rac signaling pathway. Further, we introduce a novel signaling pathway in which Rac is activated, dependent on PLCgamma and Iba1. However, to understand the molecular details of microglia activation, future work is required. (C) 2002 Wiley-Liss, Inc.