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HCMV-encoded chemokine receptor US28 employs multiple routes for internalization

Authors

  • J. Droese
  • T. Mokros
  • R. Hermosilla
  • R. Schuelein
  • M. Lipp
  • U.E. Hoepken
  • A. Rehm

Journal

  • Biochemical and Biophysical Research Communications

Citation

  • Biochem Biophys Res Commun 322 (1): 42-49

Abstract

  • 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.


DOI

doi:10.1016/j.bbrc.2004.07.076