TAILIEUCHUNG - Báo cáo khóa học: Mechanisms of internalization and recycling of the chemokine receptor, CCR5

CCR5 is a G protein-coupled receptor that binds several natural chemokines but it is alsoa coreceptor for the entryof M tropic strains of HIV-1 into cells. Levels of CCR5 on the cell surface are important for the rate ofHIV-1 infectionand 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. | Eur. J. Biochem. 271 243-252 2004 FEBS 2003 doi Mechanisms of internalization and recycling of the chemokine receptor CCR5 Anja Mueller and Philip G. Strange School of Animal and Microbial Sciences University of Reading Whiteknights Reading UK 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 C3 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. Keywords chemokine receptor CCR5 internalization recycling small G proteins Rho GTPases actin cytoskeleton. Chemokine-mediated responses are induced by the activation of G protein-coupled receptors GPCR on target cells 1 . The chemokine receptor CCR5 has been identified as a receptor for the chemokines MIP1-a MIP1-P RANTES MCP-2 MCP-3 and MCP-4 2 . CCR5 also serves as a coreceptor for the entry of M-tropic HIV-1 strains into cells 3-6 . The number of coreceptors CCR5 expressed on the cell surface is an .

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