HCMV-encoded chemokine receptor US28 employs multiple routes for internalization

Biochem Biophys Res Commun. 2004 Sep 10;322(1):42-9. doi: 10.1016/j.bbrc.2004.07.076.


The human cytomegalovirus-encoded G protein-coupled receptor homologue US28 binds inflammatory chemokines and sequesters them from the environment of infected cells. Low surface deposition and endocytosis are dependent on constitutive C-terminal phosphorylation, suggesting a requirement for beta-arrestin binding in receptor internalization. In this report, a US28-dependent redistribution of beta-arrestin into vesicular structures occurred, although internalization of US28 was independent of beta-arrestin. Internalization of US28 was dynamin-dependent, and US28 partially partitioned into the detergent-resistant membrane fraction. Endocytosis was diminished by cholesterol depletion, yet sucrose inhibition was even stronger. The relevance of the clathrin-coated pit pathway was supported by colocalization of beta(2)-adaptin and US28 in endocytic compartments. Exchange of the C-terminal dileucine endocytosis motif inhibited rapid endocytosis, indicating a direct interaction of US28 with the AP-2 adaptor complex. We suggest that the arrestin-independent, dynamin-dependent internalization of US28 reveals a differential sorting of beta-arrestins and the virally encoded chemokine receptor homologue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arrestins / metabolism*
  • Caveolae / metabolism*
  • Caveolae / ultrastructure
  • Cell Line
  • Dynamins / metabolism*
  • Endocytosis / physiology*
  • Humans
  • Kidney / cytology*
  • Kidney / metabolism*
  • Membrane Microdomains / metabolism
  • Membrane Microdomains / ultrastructure
  • Mutagenesis, Site-Directed
  • Receptors, Chemokine / metabolism*
  • Recombinant Proteins / metabolism
  • Signal Transduction / physiology
  • Tissue Distribution
  • Viral Proteins / metabolism*
  • beta-Arrestins


  • Arrestins
  • Receptors, Chemokine
  • Recombinant Proteins
  • US28 receptor, Cytomegalovirus
  • Viral Proteins
  • beta-Arrestins
  • Dynamins