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 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.
Mueller
Anja
A
School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, UK.
Strange
Philip G
PG
D036002:ADP Ribose Transferases / Q000494:pharmacology; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology; D001905:Botulinum Toxins / Q000494:pharmacology; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D016360:Clostridioides difficile; D003014:Clostridium botulinum; D006224:Cricetinae; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D022001:Focal Adhesions / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008024:Ligands; D019384:Nucleic Acid Synthesis Inhibitors; D021381:Protein Transport / Q000187:drug effects; D019713:Receptors, CCR5 / Q000378:metabolism*
D000199:Actins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; D008024:Ligands; D019384:Nucleic Acid Synthesis Inhibitors; D019713:Receptors, CCR5; C031815:toxB protein, Clostridium difficile; D015638:Cytochalasin D; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins; D019204:GTP-Binding Proteins; D002118:Calcium