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


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Galliera, E; Jala, VR; Trent, JO; Bonecchi, R; Signorelli, P; Lefkowitz, RJ; Mantovani, A; Locati, M; Haribabu, B

Published Date

  • June 11, 2004

Published In

Volume / Issue

  • 279 / 24

Start / End Page

  • 25590 - 25597

PubMed ID

  • 15084596

Pubmed Central ID

  • 15084596

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M400363200


  • eng

Conference Location

  • United States