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

Journal Article (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

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M400363200

Language

  • eng

Conference Location

  • United States