Regulation of chemotactic networks by ‘atypical’ receptors

Comerford, Iain; Litchfield, W. Reid; Harata-Lee, Yuka; Nibbs, Robert J. B.; McColl, Shaun R.

doi:10.1002/bies.20537

Cited by 53 publications

(76 citation statements)

References 73 publications

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“…Formerly known as CCR11 [33], CCXCKR is now regarded as being non-signalling and thus to be a member of the atypical family of chemokine 'receptors' [34,35]. In keeping with the lack of signalling, the DRY motif in human CCXCKR is altered to DRYVAVT.…”

Section: Ccxckrmentioning

confidence: 91%

“…In keeping with the lack of signalling, the DRY motif in human CCXCKR is altered to DRYVAVT. CCXCKR binds three homeostatic chemokines, CCL19, (Table 1), and appears to be capable of internalising these ligands and targeting them for intracellular degradation [36,37] in much the same way as is described below, in more detail, for D6 in the section In vitro studies of D6 function [34,35] (Fig. 1).…”

Section: Ccxckrmentioning

confidence: 94%

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D6 and the atypical chemokine receptor family: Novel regulators of immune and inflammatory processes

2009

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Chemokines are key regulators of leukocyte migration and play important roles in a number of physiological and pathological immune and inflammatory contexts. In addition to the classical signalling chemokine receptors there has emerged, recently, a new subclass of atypical chemokine receptors. This subfamily is characterised by an apparent lack of signalling and, in some cases, by an ability to internalise and degrade chemokine ligands. This review describes the family of atypical chemokine receptors with particular emphasis on the D6 receptor. The in vitro and in vivo biology of D6 is described, which indicates that D6 is active as a scavenger of inflammatory CC-chemokines and appears to play essential roles in the regulation of inflammatory responses.Key words: Chemokines . Immune regulation . Inflammation IntroductionThe movement of leukocytes during immune and inflammatory responses is a carefully orchestrated process that ensures coordinated cellular migration in response to physiological and pathological cues. Prominent amongst the regulators of leukocyte movement are the members of the chemokine family [1]. Chemokines are small proteins (8-12 kDa) and membership of the chemokine family is defined on the basis of the presence of variations on a conserved cysteine motif in the mature section of the proteins. Chemokines can be assigned to one of four subfamilies according to the specific nature of this motif. The majority of chemokines have four cysteines with 28 chemokines being assigned to the CC family (so-called because of the juxtaposition of the first two cysteine residues) and 16 being assigned to the CXC family (which possess a single variable amino acid between the first two cysteines). The two smaller subfamilies are represented by single members and are the CX3C family (three amino acids between the first two cyteines) and the XC family, which lacks the first and third cyteines seen in the other family members. Much confusion arose in the mid-1990s due to the complex and variable nomenclature used to refer to chemokines. For this reason a systematic nomenclature system has been adopted, which refers to the chemokines as ligands of each of the subfamilies and numbers them according to when their sequences were first deposited in the Genbank databases [2]. Thus, CCL1 is the first CC chemokine to be identified and CCL28 the most recent. Chemokines and their roles in leukocyte migrationFunctionally, chemokines are known to be pleiotropic. However, their main role is in the regulation of leukocyte migration. In this context we can define chemokines as being either homeostatic/ constitutive or inflammatory according to the contexts in which they function [2,3]. Homeostatic chemokinesThe homeostatic chemokines are important for the regulation of basal leukocyte trafficking and regulate processes such as the Mini-Reviewtissue-specific migration of T cells and the homing of DC to draining lymph nodes [4][5][6]. In combination with adhesion molecules, the homeostatic chemokines can form part of a very spec...

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Section: Ccxckrmentioning

confidence: 91%

Section: Ccxckrmentioning

confidence: 94%

D6 and the atypical chemokine receptor family: Novel regulators of immune and inflammatory processes

2009

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“…Whereas the binding of SDF1 to CXCR4 drives the migration (David et al, 2002), CXCR7 acts as an atypical receptor (Comerford et al, 2007) that may sequester SDF1 (Balabanian et al, 2005) in the trailing region of the primordium and thereby provide directionality to the migration . Alternatively or additionally, CXCR7 may contribute to migration independently of CXCR4 (Valentin et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

lef1 controls patterning and proliferation in the posterior lateral line system of zebrafish

Gamba¹,

Cubedo²,

Lutfalla³

et al. 2010

Developmental Dynamics

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The embryonic development of the posterior lateral line of zebrafish involves the migration from head to tail of a primordium comprising approximately 100 cells, and the deposition at regular intervals of presumptive mechanosensory organs (neuromasts). Migration depends on the presence of chemokine SDF1 along the pathway, and on the asymmetrical distribution of chemokine receptors CXCR4 and CXCR7 in the primordium. Primordium polarization depends on Wnt signaling in the leading region. Here, we examine the role of a major effector of Wnt signaling, lef1, in this system. We show that, although its inactivation has no overt effect on the expression of cxcr4b and cxcr7b, lef1 contributes to their control. We also show that cell proliferation, which ensures constant primordium size despite successive rounds of cell deposition, is reduced upon lef1 inactivation. Because of this defect, the primordium runs short of cells and vanishes before the line has been completed. We conclude that lef1-mediated Wnt signaling is involved in various aspects of primordium migration, although part of this implication is masked by a high level of developmental redundancy. Developmental Dynamics 239:3163-3171,

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“…This suggests the internalization of chemokines from one side of the cell and appearing them from another cell surface. 30 However, further studies confirming the CCX-CKR is necessary to support this function. Studies conducted in 2013 showed a new role for this protein.…”

Section: Ccx-ckr (Ccrl1) Proteinsmentioning

confidence: 99%

“…Because of this, cells would not polarize or migrate. 30 Atypical chemokine receptors together with normal chemokine receptors usually are expressed in wide areas and are rarely found in the blood leukocytes. These receptors also bind with different chemokines; for instance, D6 protein binds to CC and CXC.…”

Section: Silent Chemokine Receptorsmentioning

confidence: 99%