β-Arrestin-dependent Constitutive Internalization of the Human Chemokine Decoy Receptor D6*

doi:10.1074/JBC.M400363200

Paper

β-Arrestin-dependent Constitutive Internalization of the Human Chemokine Decoy Receptor D6*

Published Jun 11, 2004 · E. Galliera, V. Jala, J. Trent

Journal of Biological Chemistry

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171

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4

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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 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.

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Study Snapshot

Human D6 is a structurally adapted decoy receptor for chemokine scavenging, mediated by continuous internalization and constant surface expression, with -arrestin-dependent internalization.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

β-Arrestin-dependent Constitutive Internalization of the Human Chemokine Decoy Receptor D6*

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References

Differential Recognition and Scavenging of Native and Truncated Macrophage-Derived Chemokine (Macrophage-Derived Chemokine/CC Chemokine Ligand 22) by the D6 Decoy Receptor1

The D6 receptor efficiently recognizes and scavenges a wide spectrum of inflammatory CC chemokines, but does not engage with CD26-processed, inactive, CCL22 variants, potentially regulating CCR4-expressing cell traffic.

Lipid Bilayer Simulations of CXCR4 with Inverse Agonists and Weak Partial Agonists*

CXCR4's interaction with inverse agonist T140 and weak partial agonist AMD3100 are different, with different mechanisms used by these agents.

G-protein-coupled Receptor (GPCR) Kinase Phosphorylation and β-Arrestin Recruitment Regulate the Constitutive Signaling Activity of the Human Cytomegalovirus US28 GPCR*

US28 viral GPCR is phosphorylated by GRKs and recruits -arrestin to control multiple aspects of signal transmission, offering insights into viral pathogenesis and receptor signaling mechanisms.

The influence of Duffy blood group on renal allograft outcome in african americans

Duffy (ab) patients have lower allograft survival in African American kidney-transplant recipients, with DARC acting as a "chemokine sink" potentially protecting them from delayed graft function.

Cutting Edge: Scavenging of Inflammatory CC Chemokines by the Promiscuous Putatively Silent Chemokine Receptor D6 1

The promiscuous chemokine receptor D6 acts as a scavenger for inflammatory chemokines, potentially acting as a gatekeeper in lymphatic vessels to prevent excessive diffusion to lymph nodes.

Citations

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