Endocytosis and recycling of the HIV coreceptor CCR5.
Endocytosis and recycling of the HIV coreceptor CCR5.
复制标题
DOI：
10.1083/jcb.151.6.1281
复制
发表时间：
2000-12-11
期刊：
影响因子：
--
通讯作者：
Marsh M
中科院分区：
文献类型：
--
作者：
Signoret N;Pelchen-Matthews A;Mack M;Proudfoot AE;Marsh M
趋化因子受体CCR 5是人免疫缺陷病毒（HIV）-1和-2和猿免疫缺陷病毒的R5嗜性株进入的辅因子。对这些病毒感染敏感的细胞可以通过用活化调节的正常T细胞表达和分泌的CCR 5配体（RANTES）、MIP-1α和MIP-1β治疗来保护。趋化因子保护细胞免受HIV感染的机制的主要组成部分是诱导趋化因子受体的内吞作用。氨基氧戊烷（AOP）-RANTES，RANTES的NH 2-末端修饰形式，是R5 HIV株感染的有效抑制剂。AOP-RANTES有效地下调CCR 5的细胞表面表达，并且与RANTES相反，似乎阻止CCR 5再循环至细胞表面。在这里，我们研究这种效应的细胞基础。使用表达人CCR 5的CHO细胞，我们表明RANTES和AOP-RANTES均诱导CCR 5的快速内化。在配体不存在的情况下，CCR 5显示组成型周转，半衰期为6-9 h。RANTES或AOP-RANTES的添加对CCR 5周转率的影响很小。免疫荧光和免疫电子显微镜显示，RANTES或AOP-RANTES治疗后，大多数CCR 5内化积累在细胞核周区域聚集的小膜结合囊泡和小管中。与转铁蛋白受体共定位在相同的囊泡簇中表明CCR 5在再循环内体中积累。去除RANTES后，内化的CCR 5粘附到细胞表面，并对RANTES诱导的内吞作用敏感。相反，在去除AOP-RANTES后，大多数CCR 5保留在细胞内。我们表明，这些CCR 5分子循环到细胞表面，与RANTES处理的细胞中的受体的动力学相当。然而，这些回收的CCR 5分子迅速重新内化。我们的研究结果表明，AOP-RANTES诱导的CCR 5的变化改变了受体的稳态分布，并提供了第一个证据G蛋白偶联受体通过回收内体室运输。
The chemokine receptor CCR5 is a cofactor for the entry of R5 tropic strains of human immunodeficiency viruses (HIV)-1 and -2 and simian immunodeficiency virus. Cells susceptible to infection by these viruses can be protected by treatment with the CCR5 ligands regulated on activation, normal T cell expressed and secreted (RANTES), MIP-1α, and MIP-1β. A major component of the mechanism through which chemokines protect cells from HIV infection is by inducing endocytosis of the chemokine receptor. Aminooxypentane (AOP)-RANTES, an NH2-terminal modified form of RANTES, is a potent inhibitor of infection by R5 HIV strains. AOP-RANTES efficiently downmodulates the cell surface expression of CCR5 and, in contrast with RANTES, appears to prevent recycling of CCR5 to the cell surface. Here, we investigate the cellular basis of this effect. Using CHO cells expressing human CCR5, we show that both RANTES and AOP-RANTES induce rapid internalization of CCR5. In the absence of ligand, CCR5 shows constitutive turnover with a half-time of 6–9 h. Addition of RANTES or AOP-RANTES has little effect on the rate of CCR5 turnover. Immunofluorescence and immunoelectron microscopy show that most of the CCR5 internalized after RANTES or AOP-RANTES treatment accumulates in small membrane-bound vesicles and tubules clustered in the perinuclear region of the cell. Colocalization with transferrin receptors in the same clusters of vesicles indicates that CCR5 accumulates in recycling endosomes. After the removal of RANTES, internalized CCR5 recycles to the cell surface and is sensitive to further rounds of RANTES-induced endocytosis. In contrast, after the removal of AOP-RANTES, most CCR5 remains intracellular. We show that these CCR5 molecules do recycle to the cell surface, with kinetics equivalent to those of receptors in RANTES-treated cells. However, these recycled CCR5 molecules are rapidly reinternalized. Our results indicate that AOP-RANTES–induced changes in CCR5 alter the steady-state distribution of the receptor and provide the first evidence for G protein–coupled receptor trafficking through the recycling endosome compartment.
登录
查看更多内容
DOI：
10.1083/jcb.109.6.2703
发表时间：
1989-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Griffiths G;Back R;Marsh M
通讯作者：
Marsh M
影响因子：
15.3
作者：
Amara, A;LeGall, S;Schwartz, O;Salamero, J;Montes, M;Loetscher, P;Baggiolini, M;Virelizier, JL;ArenzanaSeisdedos, F
通讯作者：
ArenzanaSeisdedos, F
DOI：
10.1084/jem.187.8.1215
发表时间：
1998-04-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mack M;Luckow B;Nelson PJ;Cihak J;Simmons G;Clapham PR;Signoret N;Marsh M;Stangassinger M;Borlat F;Wells TN;Schlöndorff D;Proudfoot AE
通讯作者：
Proudfoot AE
影响因子：
56.9
作者：
COCCHI, F;DEVICO, AL;LUSSO, P
通讯作者：
LUSSO, P
DOI：
10.1073/pnas.82.10.3197
发表时间：
1985-01-01
影响因子：
11.1
作者：
ESKO, JD;STEWART, TE;TAYLOR, WH
通讯作者：
TAYLOR, WH