The 73-kDa heat shock cognate protein is a CXCR4 binding protein that regulates the receptor endocytosis and the receptor-mediated chemotaxis
The 73-kDa heat shock cognate protein is a CXCR4 binding protein that regulates the receptor endocytosis and the receptor-mediated chemotaxis
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DOI：
10.1124/mol.105.020271
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发表时间：
2006-04-01
影响因子：
3.6
通讯作者：
Fan, GH
中科院分区：
文献类型：
--
作者：
Ding, Y;Li, M;Fan, GH
CXCR 4趋化因子受体是一种G蛋白偶联受体，在白细胞归巢、癌症转移和人类免疫缺陷病毒感染中起重要作用。趋化因子受体对配体刺激的反应是通过网格蛋白包被的囊泡（CCV）进行内吞。CCV的脱壳是一个涉及热休克同源蛋白和其他几种蛋白质的过程，对于CCV融合到内体区室至关重要。目前的研究表明，CXCR 4与73 kDa的热休克同源蛋白（Hsc 73）在人胚肾293细胞在响应配体刺激。截断CXCR 4的羧基末端结构域减少与Hsc 73和谷胱甘肽S-转移酶-CXCR 4的羧基末端融合蛋白与Hsc 73在体外，表明参与的相互作用的受体的羧基末端结构域。在配体刺激下，CXCR 4与Hsc 73发生内化和共定位，但通过RNA干扰敲低Hsc 73可阻断CXCR 4的内吞作用。此外，Hsc 73敲低显著降低了CXCR 4介导的U87胶质瘤细胞系的趋化性。这些结果表明，Hsc 73在趋化因子受体运输和受体介导的趋化性中发挥作用。
The CXCR4 chemokine receptor is a G protein-coupled receptor that plays an important role in leukocyte homing, cancer metastasis, and human immunodeficiency virus infection. In response to ligand stimulation, chemokine receptors undergo endocytosis through clathrin-coated vesicle (CCV). Uncoating of CCV, a process involving heat shock cognate protein and several other proteins, is critical for fusion of CCV to endosomal compartments. The present study demonstrated that CXCR4 was associated with the 73-kDa heat shock cognate protein (Hsc73) in human embryonic kidney 293 cells in response to ligand stimulation. Truncation of the carboxyl terminal domain of CXCR4 reduced the association with Hsc73 and a glutathione S-transferase-CXCR4 carboxyl terminal fusion protein associated with Hsc73 in vitro, suggesting involvement of the carboxyl terminal domain of the receptor in the interaction. In response to ligand stimulation, CXCR4 underwent internalization and colocalization with Hsc73, but the receptor endocytosis was blocked by knockdown of Hsc73 with RNA interference. Moreover, Hsc73 knockdown significantly reduced the CXCR4-mediated chemotaxis of U87 glioma cell lines. These findings suggest that Hsc73 plays a role in chemokine receptor trafficking and the receptor-mediated chemotaxis.