MTOC reorientation occurs during FcgammaR-mediated phagocytosis in macrophages.

MTOC reorientation occurs during FcgammaR-mediated phagocytosis in macrophages.
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DOI:
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发表时间:
2007
影响因子:
3.3
通讯作者:
Edward W. Y. Eng;Adam N. Bettio;J. Ibrahim;R. Harrison
Edward W. Y. Eng;Adam N. Bettio;J. Ibrahim;R. Harrison
中科院分区:
生物学3区
文献类型:
--
作者:
Edward W. Y. Eng;Adam N. Bettio;J. Ibrahim;R. Harrison

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细胞极化对于将信号元件和细胞器靶向活性质膜区域至关重要。在一些特殊的细胞类型中,通过将 MTOC 和相关细胞器重新定向到动态膜位点来增强细胞极性。吞噬作用是一个高度极化的过程,其中 >0.5 微米的颗粒在巨噬细胞细胞表面的刺激区域内化。在这里,我们提供了详细的证据,证明 MTOC 在吞噬过程中重新定向到颗粒内化的位点。在活细胞成像过程中,我们使用荧光嵌合体标记 MTOC 并使用受挫吞噬实验,观察了固定 RAW264.7 细胞中 MTOC 与 IgG-sRBC 的接近程度。巨噬细胞中的 MTOC 重新定向是由 FcgammaR 连接启动的,并在 1 小时内完成。 MTOC 向吞噬体的极化需要 MT 细胞骨架和动力蛋白运动活性。 cdc42、PI3K 和 mPAR-6 都是吞噬过程中 MTOC 重新定向的重要信号分子。 MTOC 重新定向对于颗粒内化或吞噬溶酶体形成并不重要。然而,吞噬作用过程中高尔基体重新定向与 MTOC 重新定向相一致,暗示巨噬细胞中抗原加工事件中 MTOC 重新定向。
Cell polarization is essential for targeting signaling elements and organelles to active plasma membrane regions. In a few specialized cell types, cell polarity is enhanced by reorientation of the MTOC and associated organelles toward dynamic membrane sites. Phagocytosis is a highly polarized process whereby particles >0.5 microm are internalized at stimulated regions on the cell surface of macrophages. Here we provide detailed evidence that the MTOC reorients toward the site of particle internalization during phagocytosis. We visualized MTOC proximity to IgG-sRBCs in fixed RAW264.7 cells, during live cell imaging using fluorescent chimeras to label the MTOC and using frustrated phagocytosis assays. MTOC reorientation in macrophages is initiated by FcgammaR ligation and is complete within 1 h. Polarization of the MTOC toward the phagosome requires the MT cytoskeleton and dynein motor activity. cdc42, PI3K, and mPAR-6 are all important signaling molecules for MTOC reorientation during phagocytosis. MTOC reorientation was not essential for particle internalization or phagolysosome formation. However Golgi reorientation in concert with MTOC reorientation during phagocytosis implicates MTOC reorientation in antigen processing events in macrophages.