Rap1 activation is required for Fc gamma receptor-dependent phagocytosis.
Rap1 activation is required for Fc gamma receptor-dependent phagocytosis.
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DOI：
10.4049/jimmunol.181.8.5501
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发表时间：
2008-10-15
期刊：
影响因子：
--
通讯作者：
Peters-Golden M
中科院分区：
文献类型：
--
作者：
Chung J;Serezani CH;Huang SK;Stern JN;Keskin DB;Jagirdar R;Brock TG;Aronoff DM;Peters-Golden M
通过Fcγ受体（FcγR）吞噬IgG调理的微生物需要许多信号分子（包括低分子量GTP酶）的精确协调。在这一过程中，对Ras家族的GTIPRRAP 1知之甚少。因此，我们研究了它在NR 8383大鼠肺泡巨噬细胞介导Fcγ R依赖性吞噬作用中的重要性。对转染GFP-RalGDS（Ral guanine dissociation stimulator）的巨噬细胞的活性Rap 1的下拉和荧光显微镜分析显示，Rap 1确实被FcγR交联激活。Rap 1活性的抑制，无论是Rap 1GAP（GTP酶激活蛋白）的表达和脂质体递送的阻断抗体，严重损害了细胞摄取IgG调理目标的能力。Fcγ R诱导的Rap 1激活不依赖于cAMP和Ca 2+，表明第二个信使非依赖性鸟苷交换因子C3 G的作用。这一点得到以下事实的支持：1）脂质体递送的针对C3 G的阻断性Ab抑制Fcγ R依赖的吞噬作用和Rap 1活化，2）发现活性Rap 1GTP和C3 G均移位到吞噬体。综上所述，我们的数据表明Rap 1及其交换因子C3 G在介导Fcγ R依赖性吞噬作用中的新作用。
Phagocytosis of IgG-opsonized microbes via the Fcγ receptor (FcγR) requires the precise coordination of a number of signaling molecules, including the low-molecular mass GTPases. Little is known about the Ras-family GTPase Rap1 in this process. We therefore investigated its importance in mediating FcγR-dependent phagocytosis in NR8383 rat alveolar macrophages. Pulldown of active Rap1 and fluorescence microscopic analysis of GFP-RalGDS (Ral guanine dissociation stimulator)-transfected macrophages revealed that Rap1 is indeed activated by FcγR crosslinking. Inhibition of Rap1 activity, both by Rap1GAP (GTPase-activating protein) expression and liposome-delivered blocking Ab, severely impaired the ability of cells to ingest IgG-opsonized targets. FcγR-induced Rap1 activation was found to be independent of both cAMP and Ca2+, suggesting a role for the second messenger-independent guanosine exchange factor, C3G. This was supported by the facts that 1) liposome-delivered blocking Ab against C3G inhibited both FcγR-dependent phagocytosis and Rap1 activation, and 2) both active Rap1GTP and C3G were found to translocate to the phagosome. Taken together, our data demonstrate a novel role for Rap1 and its exchange factor C3G in mediating FcγR-dependent phagocytosis.
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作者：
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DOI：
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