Mechanisms of internalization and recycling of the chemokine receptor, CCR5
Mechanisms of internalization and recycling of the chemokine receptor, CCR5
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DOI：
10.1046/j.1432-1033.2003.03918.x
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Strange, PG
中科院分区：
文献类型：
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作者：
Mueller, A;Strange, PG
CCR 5是一种G蛋白偶联受体，可结合几种天然趋化因子，但它也是HIV-1嗜M性毒株进入细胞的辅助受体。细胞表面的CCR 5水平对HIV-1感染率很重要，并由许多因素决定，包括CCR 5内化和再循环的速率。在这里，我们研究了肌动蛋白细胞骨架参与配体诱导的CCR 5的内化和回收的控制。细胞松弛素D，一种肌动蛋白解聚剂，抑制趋化因子诱导的CCR 5的内化和稳定转染的CHO细胞和单核细胞系THP-1中受体的再循环。在CHO和THP-1细胞中，毒素B和C-3外切酶处理抑制了CCR 5内化和再循环，证实了CCR 5激活了RhoGT 3家族成员。然而，特异性Rho激酶抑制剂Y27632对CCR 5内化或再循环没有影响。配体诱导的CCR 5活化导致粘着斑复合物的Rho激酶依赖性形成。这些数据表明，CCR 5的内化和回收调节肌动蛋白聚合和激活的小G蛋白在一个Rho依赖性的方式。
CCR5 is a G protein-coupled receptor that binds several natural chemokines but it is also a coreceptor for the entry of M tropic strains of HIV-1 into cells. Levels of CCR5 on the cell surface are important for the rate of HIV-1 infection and are determined by a number of factors including the rates of CCR5 internalization and recycling. Here we investigated the involvement of the actin cytoskeleton in the control of ligand-induced internalization and recycling of CCR5. Cytochalasin D, an actin depolymerizing agent, inhibited chemokine-induced internalization of CCR5 and recycling of the receptor in stably transfected CHO cells and in the monocytic cell line, THP-1. CCR5 internalization and recycling were inhibited by Toxin B and C-3 exoenzyme treatment in CHO and THP-1 cells, confirming activation of members of the RhoGTPase family by CCR5. The specific Rho kinase inhibitor Y27632, however, had no effect on CCR5 internalization or recycling. Ligand-induced activation of CCR5 leads to Rho kinase-dependent formation of focal adhesion complexes. These data indicate that CCR5 internalization and recycling are regulated by actin polymerization and activation of small G proteins in a Rho-dependent manner.