Comparisons of CapG and gelsolin-null macrophages: demonstration of a unique role for CapG in receptor-mediated ruffling, phagocytosis, and vesicle rocketing.
Comparisons of CapG and gelsolin-null macrophages: demonstration of a unique role for CapG in receptor-mediated ruffling, phagocytosis, and vesicle rocketing.
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DOI：
10.1083/jcb.200101113
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发表时间：
2001-08-20
影响因子：
7.8
通讯作者：
Southwick, F S
中科院分区：
文献类型：
--
作者：
Witke, W;Li, W;Kwiatkowski, D J;Southwick, F S
在非肌肉细胞中，给肌动蛋白丝的倒刺末端加帽是调节肌动蛋白运动的关键步骤。CapG是一种钙敏感的倒刺末端加帽蛋白，是凝溶胶蛋白/绒毛蛋白家族的成员，其体内功能已使用工程化到小鼠中的无效Capg等位基因进行了评估。CapG缺失小鼠和CapG/凝溶胶蛋白双缺失小鼠均表现正常，没有明显的功能异常。然而，CapG在骨髓巨噬细胞中的损失深刻地抑制巨噬细胞集落刺激因子刺激的皱褶;通过显微注射重新引入CapG蛋白完全恢复这一功能。CapG-空巨噬细胞也表现出免疫球蛋白G，补体调理吞噬作用和镧诱导的囊泡火箭损伤超过50%。这些运动功能在无凝溶胶蛋白的巨噬细胞中没有受损，并且在CapG/凝溶胶蛋白双无效巨噬细胞中没有观察到累加效应，从而确定CapG功能与巨噬细胞中的凝溶胶蛋白不同，并且不重叠。我们的观察表明，CapG是所需的受体介导的皱褶，它是一个主要的功能组成部分，巨噬细胞吞噬。这些对巨噬细胞运动功能的主要作用表明CapG可能是调节巨噬细胞介导的炎症反应的有用靶点。
Capping the barbed ends of actin filaments is a critical step for regulating actin-based motility in nonmuscle cells. The in vivo function of CapG, a calcium-sensitive barbed end capping protein and member of the gelsolin/villin family, has been assessed using a null Capg allele engineered into mice. Both CapG-null mice and CapG/gelsolin double-null mice appear normal and have no gross functional abnormalities. However, the loss of CapG in bone marrow macrophages profoundly inhibits macrophage colony stimulating factor–stimulated ruffling; reintroduction of CapG protein by microinjection fully restores this function. CapG-null macrophages also demonstrate ∼50% impairment of immunoglobulin G, and complement-opsonized phagocytosis and lanthanum-induced vesicle rocketing. These motile functions are not impaired in gelsolin-null macrophages and no additive effects are observed in CapG/gelsolin double-null macrophages, establishing that CapG function is distinct from, and does not overlap with, gelsolin in macrophages. Our observations indicate that CapG is required for receptor-mediated ruffling, and that it is a major functional component of macrophage phagocytosis. These primary effects on macrophage motile function suggest that CapG may be a useful target for the regulation of macrophage-mediated inflammatory responses.