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.
beta-Arrestin-dependent constitutive internalization of the human chemokine decoy receptor D6 / E. Galliera, V.R. Jala, J.O. Trent, R. Bonecchi, P. Signorelli, R.J. Lefkowitz, A. Mantovani, M. Locati, B. Haribabu. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 279:24(2004 Jun 11), pp. 25590-25597. [10.1074/jbc.M400363200]
beta-Arrestin-dependent constitutive internalization of the human chemokine decoy receptor D6
E. GallieraPrimo
;R. Bonecchi;P. Signorelli;A. Mantovani;M. LocatiPenultimo
;
2004
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.Pubblicazioni consigliate
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