beta-Arrestin-dependent constitutive internalization of the human chemokine decoy receptor D6

J Biol Chem. 2004 Jun 11;279(24):25590-7. doi: 10.1074/jbc.M400363200. Epub 2004 Apr 13.

Abstract

Seven transmembrane receptors mediate diverse physiological responses including hormone action, olfaction, neurotransmission, and chemotaxis. Human D6 is a non-signaling seven-transmembrane receptor expressed on lymphatic endothelium interacting with most inflammatory CC-chemokines resulting in their rapid internalization. Here, we demonstrate that this scavenging activity is mediated by continuous internalization and constant surface expression of the receptor, a process involving the clathrin-coated pit-dependent pathway. D6 constitutively associates with the cytoplasmic adaptor beta-arrestin, and this interaction is essential for D6 internalization. An acidic region, but not the putative phosphorylation sites in the cytoplasmic tail of D6, is critical for receptor interaction with beta-arrestin and subsequent internalization. Neither the native D6 nor mutants uncoupled from beta-arrestin activate any G-protein-mediated signaling pathways. Therefore, D6 may be considered a decoy receptor structurally adapted to perform chemokine scavenging.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arrestins / chemistry
  • Arrestins / physiology*
  • Binding Sites
  • CHO Cells
  • Chemokine Receptor D6
  • Cricetinae
  • Humans
  • Molecular Sequence Data
  • Receptors, CCR10
  • Receptors, Chemokine / chemistry
  • Receptors, Chemokine / metabolism*
  • beta-Arrestins

Substances

  • Arrestins
  • Receptors, CCR10
  • Receptors, Chemokine
  • beta-Arrestins