A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages.
A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages.
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DOI：
10.1083/jcb.135.5.1249
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发表时间：
1996-12
影响因子：
7.8
通讯作者：
Swanson, JA
中科院分区：
文献类型：
--
作者：
Araki, N;Johnson, MT;Swanson, JA
磷脂酰肌醇3-激酶(PI-3-Kinase)参与了生长因子信号转导和囊泡膜运输。它被认为是导致细胞表面受体结扎到增加细胞表面褶皱的最早步骤的中介。我们在这里表明，PI 3-激酶的抑制剂抑制巨噬细胞的内吞作用，不是通过干扰这一过程的启动，而是通过阻止其完成。与早期研究一致，抑制剂Wortmannin和LY294002抑制液相吞饮和Fc受体介导的吞噬作用，但对DII标记的乙酰化低密度脂蛋白受体介导的吞噬作用几乎没有影响。大的内吞的溶质探针比小的探针对Wortmannin的抑制作用更强，这表明大的胞吞作用比小的胞饮作用受到的影响更大。由于巨噬细胞吞噬和吞噬是肌动蛋白介导的过程，我们推测Wortmannin对它们的抑制是由于巨噬细胞集落刺激因子(M-CSF)受体或Fc受体对肌动蛋白细胞骨架的信号传递不足所致。然而，视频显微镜显示，Wortmannin处理的细胞表面出现褶皱，在加入M-CSF或佛波醇肉豆蔻酸醋酸酯后，褶皱增加。视频数据的定量测量报告说，在Wortmannin处理的细胞中，褶皱略有减少。值得注意的是，在Wortmannin处理的巨噬细胞中形成的褶皱都退缩到细胞质中，而不是靠近大针体。同样，Wortmannin和LY294002不能抑制富含肌动蛋白的伪足沿着免疫球蛋白调理的绵羊红细胞延伸，而是阻止它们接近吞噬小体。这些发现表明，PI-3-K不是受体介导的伪足伸展刺激所必需的，而是在关闭大胞体和吞噬体进入细胞内细胞器中起作用。
Phosphoinositide 3-kinase (PI 3-kinase) has been implicated in growth factor signal transduction and vesicular membrane traffic. It is thought to mediate the earliest steps leading from ligation of cell surface receptors to increased cell surface ruffling. We show here that inhibitors of PI 3-kinase inhibit endocytosis in macrophages, not by interfering with the initiation of the process but rather by preventing its completion. Consistent with earlier studies, the inhibitors wortmannin and LY294002 inhibited fluid-phase pinocytosis and Fc receptor-mediated phagocytosis, but they had little effect on the receptor-mediated endocytosis of diI-labeled, acetylated, low density lipoprotein. Large solute probes of endocytosis reported greater inhibition by wortmannin than smaller probes did, indicating that macropinocytosis was affected more than micropinocytosis. Since macropinocytosis and phagocytosis are actin-mediated processes, we expected that their inhibition by wortmannin resulted from deficient signaling from macrophage colony-stimulating factor (M-CSF) receptors or Fc receptors to the actin cytoskeleton. However, video microscopy showed cell surface ruffling in wortmannin-treated cells, and increased ruffling after addition of M-CSF or phorbol myristate acetate. Quantitative measurements of video data reported slightly diminished ruffling in wortmannin-treated cells. Remarkably, the ruffles that formed in wortmannin-treated macrophages all receded into the cytoplasm without closing into macropinosomes. Similarly, wortmannin and LY294002 did not inhibit the extension of actin-rich pseudopodia along IgG- opsonized sheep erythrocytes, but instead prevented them from closing into phagosomes. These findings indicate that PI 3-kinase is not necessary for receptor-mediated stimulation of pseudopod extension, but rather functions in the closure of macropinosomes and phagosomes into intracellular organelles.
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磷脂酰肌醇3-激酶在哺乳动物细胞中新合成溶酶体酶的分选和转运中的作用。
影响因子：
7.8
作者：
BROWN, WJ;DEWALD, DB;EMR, SD;PLUTNER, H;BALCH, WE
通讯作者：
BALCH, WE
影响因子：
11.4
作者：
CARLBERG, K;TAPLEY, P;ROHRSCHNEIDER, L
通讯作者：
ROHRSCHNEIDER, L
影响因子：
11.4
作者：
KOTANI, K;YONEZAWA, K;KASUGA, M
通讯作者：
KASUGA, M
DOI：
10.1073/pnas.92.12.5317
发表时间：
1995-06-06
影响因子：
11.1
作者：
NAKANISHI, S;CATT, KJ;BALLA, T
通讯作者：
BALLA, T
影响因子：
56.9
作者：
SCHU, PV;TAKEGAWA, K;EMR, SD
通讯作者：
EMR, SD