Multiple roles for the C-terminal tail of the chemokine scavenger D6.

Abstract

PAGE 7977:The original version of Fig. 4 contained an error. The same image was used in the "wtD6" and "D6-Ala6" panels. We have now replaced the "D6-Ala6" panel with the correct image. This revision does not change the results or the interpretation of the data.

International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors

“…Biochemically, ACKR2 is sulfated on N-terminal tyrosine residues and possesses a single N-terminal glycosylation site that is not required for function . In contrast to other chemokine receptors, which require ligand binding to induce phosphorylation, ACKR2 appears to be constitutively phosphorylated on the intracellular Cterminal domain, suggesting that it is in a permanently active configuration with regard to receptor internalization and recycling (McCulloch et al, 2008).…”

The Atypical Chemokine Receptors

“…While there is agreement that it enters cells via clathrin-coated pits (CCPs), the role of b-arrestins, which direct many G proteincoupled receptors to CCPs, is unclear. We have found that constitutive phosphorylation of a serine cluster in the C-terminus of D6 drives b-arrestins to the cell surface in D6-expressing cells, and controls intracellular trafficking itineraries, but we also showed that this is dispensable for chemokine scavenging [17]. Instead, in our hands, a helical region in the C-terminal tail adjacent to the seventh transmembrane helix was critical for scavenging [17].…”

“…We have found that constitutive phosphorylation of a serine cluster in the C-terminus of D6 drives b-arrestins to the cell surface in D6-expressing cells, and controls intracellular trafficking itineraries, but we also showed that this is dispensable for chemokine scavenging [17]. Instead, in our hands, a helical region in the C-terminal tail adjacent to the seventh transmembrane helix was critical for scavenging [17]. Others reported that an acidic region at the other end of the C-terminal tail mediated constitutive interactions with b-arrestins and that these interactions were required for D6 internalization [14].…”

Lipid‐Embedded Molecular Dynamics Simulation Model for Exploring the Reverse Prostaglandin D2 Agonism of CT‐133 towards CRTH2 in the Treatment of Type‐2 Inflammation Dependent Diseases

“…The C-termini region of GPCRs has emerged as a critical structure in regulating several phases of their functions including dimerization, [67] expression, [68] signaling, [68 -70] trafficking, [71] and binding to regulatory proteins of the arrestin family. [72,73] Helix 8 is a distinctive long helical structure in the C-terminal region of several GCPRs including class A Rhodopsinlike family [63] and CRTH2.…”