Disease relevance of CCRL1

• Several chemokine receptors and chemokine receptor-like orphan receptors also serve, in conjunction with CD4, as coreceptors for infection by human and simian immunodeficiency viruses (HIV and SIV) [1].
• CONCLUSION: These observations implicate CCX CKR in the modulation of the inflammatory response in sarcoidosis [2].
• Expression of CCX CKR in pulmonary sarcoidosis [2].
• Circulating clonal CLA(+) and CD4(+) T cells in Sezary syndrome express the skin-homing chemokine receptors CCR4 and CCR10 as well as the lymph node-homing chemokine receptor CCR7 [3].
• cytoplasmic male sterility of rice with boro II cytoplasm is caused by a cytotoxic peptide and is restored by two related PPR motif genes via distinct modes of mRNA silencing [4].
• Lack or low expression of CCX-CKR correlated with a poor survival rate in the breast cancer patients [5].

High impact information on CCRL1

• An update of the International Union of Pharmacology nomenclature for chemokines is outlined, defining one new receptor type, CXCR6, and disqualifying the putative receptor, CCR11 [6].
• Few T cells in any mucosal tissue examined express CCR10 [7].
• Here we demonstrate that CCR10, a receptor for MEC, is selectively expressed by IgA Ab-secreting cells (large s/cIgA(+)CD38(hi)CD19(int/-)CD20(-)), including circulating IgA(+) plasmablasts and almost all IgA(+) plasma cells in the salivary gland, small intestine, large intestine, appendix, and tonsils [7].
• Unlike other C6 zinc cluster proteins such as GAL4 and PPR1, HAP1 binds selectively to asymmetric DNA sites containing a direct repeat of two CGG triplets [8].
• These receptor clones will be useful in elucidating the functional role of PP and designing selective PP receptor agonists and antagonists [9].

Biological context of CCRL1

• We report here on human CCX CKR, previously represented only by noncontiguous expressed sequence tags homologous to bovine PPR1, a putative gustatory receptor [10].
• However, in man, there are two copies of the CCX-CKR gene, one on chromosome 3 nestled within the ACD homologue, and one on chromosome 6 [11].
• CCX-CKR cannot couple to typical chemokine receptor signalling pathways or mediate chemotaxis, and its function remains unclear [12].
• The gene for CCR11 was localized to human chromosome 3q22, which is distinct from most CC chemokine receptor genes at 3p21 [13].
• CCX CKR transcripts were upregulated in patients (mean +/- SEM); S, 0.82 +/- 0.10; C, 0.44 +/- 0.04; p = 0.01; this upregulation paralleled the disease course as assessed by the chest radiographic stage (p < 0.02) [2].

Anatomical context of CCRL1

• In-situ hybridization confirmed the presence of CCRL1 mRNA in cardiac muscle cells [14].
• Interestingly, in brain and testis, an alternative mRNA form of CCX-CKR exists with a unique 5' untranslated region (5'UTR) that overlaps with a novel acyl-CoA dehydrogenase (ACD) gene [11].
• Northern blot hybridization was used to identify CCR11 expression in heart, small intestine, and lung [13].
• CCR10 is found on skin-homing T cells and also directs IgA-producing plasma cells into mucosal sites [15].
• The CC chemokine receptors CCR6, CCR9, and CCR10 all contribute to the positioning of leukocytes at mucosal locations [15].

Associations of CCRL1 with chemical compounds

• Unlike most other chemokine receptors, CCX-CKR is unable to mediate Ca(2+) fluxes upon ligand binding when expressed in HEK293 cells [11].

Other interactions of CCRL1

• However, internalised CCL19 was more efficiently retained and degraded after uptake via CCX-CKR [12].
• Because these data may identify the receptor as primarily a PP receptor, we have named it PP1 [16].
• RFamides could act both as ligands of membrane neighbors of the PP receptor, and as competitors of Y5-like NPY receptor epitopes that accommodate the C-terminal aspects of agonist peptides [17].

Analytical, diagnostic and therapeutic context of CCRL1

• Murine CCX-CKR is expressed predominantly in the heart and lung, but is detectable in most organs using RT-PCR [11].
• Immunocytochemistry localised the CCX CKR protein to ciliated bronchial cells [2].

References