β-arrestin-dependent constitutive internalization of the human chemokine decoy receptor D6

Emanuela Galliera, Venkatakrishna R. Jala, John O. Trent, Raffaella Bonecchi, Paola Signorelli, Robert J. Lefkowitz, Alberto Mantovani, Massimo Locati, Bodduluri Haribabu

Research output: Contribution to journalArticlepeer-review

Abstract

Seven transmembrane receptors mediate diverse physiological responses including hormone action, o1-faction, 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 β-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 β-arrestin and subsequent internalization. Neither the native D6 nor mutants uncoupled from β-arrestin activate any G-protein-mediated signaling pathways. Therefore, D6 may be considered a decoy receptor structurally adapted to perform chemokine scavenging.

Original languageEnglish
Pages (from-to)25590-25597
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number24
DOIs
Publication statusPublished - Jun 11 2004

ASJC Scopus subject areas

  • Biochemistry

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