Mechanisms of internalization and recycling of the chemokine receptor, CCR5

Authors

  • Anja Mueller,

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    • Present address: Leukocyte Biology Section, Division of Biomedical Sciences, Imperial College London, Faculty of Medicine, Sir Alexander Fleming Building, Exhibition Road, London SW7 2AZ, UK.

  • Philip G. Strange

    1. School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, UK
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P. G. Strange, School of Animal and Microbial Sciences, University of Reading, PO Box 228, Reading, RG6 6AJ, UK. Fax: + 44 118378 6537, Tel.: + 44 118378 8015,
E-mail: P.G.Strange@rdg.ac.uk

Abstract

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.

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