CX3CR1

Chemokine (C-X3-C motif) receptor 1
Identifiers
Symbols	CX3CR1 ; CCRL1; CMKBRL1; CMKDR1; GPR13; GPRV28; V28
External IDs	OMIM: 601470 MGI: 1333815 HomoloGene: 20350 IUPHAR: 74 ChEMBL: 4843 GeneCards: CX3CR1 Gene
Gene ontology Molecular function • chemokine receptor activity • protein binding • C-X3-C chemokine receptor activity Cellular component • plasma membrane • integral component of plasma membrane • neuronal cell body membrane • neuron projection • perinuclear region of cytoplasm Biological process • positive regulation of neuroblast proliferation • microglial cell activation involved in immune response • negative regulation of chronic inflammatory response to non-antigenic stimulus • chemotaxis • cellular defense response • cell adhesion • G-protein coupled receptor signaling pathway • memory • response to wounding • viral process • negative regulation of angiogenesis • cerebral cortex cell migration • negative regulation of cell migration • positive regulation of angiogenesis • macrophage chemotaxis • chemokine-mediated signaling pathway • cellular response to lipopolysaccharide • cellular response to transforming growth factor beta stimulus • negative regulation of long-term synaptic potentiation • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1524	13051
Ensembl	ENSG00000168329	ENSMUSG00000052336
UniProt	P49238	Q9Z0D9
RefSeq (mRNA)	NM_001171171	NM_009987
RefSeq (protein)	NP_001164642	NP_034117
Location (UCSC)	Chr 3: 39.26 – 39.28 Mb	Chr 9: 119.9 – 120.07 Mb
PubMed search

CX3C chemokine receptor 1 (CX3CR1) also known as the fractalkine receptor or G-protein coupled receptor 13 (GPR13) is a protein that in humans is encoded by the CX3CR1 gene.^[1][2] As the name suggests, this receptor binds the chemokine CX3CL1 (also called neurotactin or fractalkine).

Function

The fractalkine ligand CX3CL1 is a transmembrane protein and chemokine involved in the adhesion and migration of leukocytes. The protein encoded by the CX3R1 gene is a receptor for the fractalkine ligand.^[3]

Expression of this receptor appears to be associated with lymphocytes.^[4] CX3CR1 is also expressed by monocytes and plays a major role in the survival of monocytes.

Fractalkine signalling has also recently been discovered to play a developmental role in the migration of microglia in the central nervous system to their synaptic targets, where phagocytosis and synaptic refinement occur. CX3CR1 knockout mice had more synapses on cortical neurons than wild-type mice.

Clinical significance

CX3CR1 also is a coreceptor for HIV-1, and some variations in this gene lead to increased susceptibility to HIV-1 infection and rapid progression to AIDS.^[3]

CX3CR1 variants have been described to modify the survival time and the progression rate of patients with amyotrophic lateral sclerosis.^[5]

Mutations in CX3CR1 are associated to dysplasia of the hip .^[6]

References

1. Combadiere C, Ahuja SK, Murphy PM (Aug 1995). "Cloning, chromosomal localization, and RNA expression of a human beta chemokine receptor-like gene". DNA and Cell Biology 14 (8): 673–80. doi:10.1089/dna.1995.14.673. PMID 7646814.
2. Combadiere C, Salzwedel K, Smith ED, Tiffany HL, Berger EA, Murphy PM (Sep 1998). "Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1". The Journal of Biological Chemistry 273 (37): 23799–804. doi:10.1074/jbc.273.37.23799. PMID 9726990.
3. "Entrez Gene: chemokine (C-X3-C motif) receptor 1".
4. Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O (Nov 1997). "Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion". Cell 91 (4): 521–30. doi:10.1016/S0092-8674(00)80438-9. PMID 9390561.
5. Lopez-Lopez, Alan; Gamez, Josep; Syriani, Emilio; Morales, Miguel; Salvado, Maria; Rodríguez, Manuel J.; Mahy, Nicole; Vidal-Taboada, Jose M. (7 May 2014). "CX3CR1 Is a Modifying Gene of Survival and Progression in Amyotrophic Lateral Sclerosis". PLOS ONE. doi:10.1371/journal.pone.009652.
6. Feldman GJ, Parvizi J, Sawan H, Erickson JA, Peters CL (Sep 2014). "Linkage mapping and whole exome sequencing identify a shared variant in CX3CR1 in a large multi-generation family". The Journal of Arthroplasty 29 (9 Suppl): 238–41. doi:10.1016/j.arth.2014.05.014. PMID 24998320.

Further reading

• Robertson MJ (Feb 2002). "Role of chemokines in the biology of natural killer cells". Journal of Leukocyte Biology 71 (2): 173–83. PMID 11818437.
• Raport CJ, Schweickart VL, Eddy RL, Shows TB, Gray PW (Oct 1995). "The orphan G-protein-coupled receptor-encoding gene V28 is closely related to genes for chemokine receptors and is expressed in lymphoid and neural tissues". Gene 163 (2): 295–9. doi:10.1016/0378-1119(95)00336-5. PMID 7590284.
• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Mizoue LS, Bazan JF, Johnson EC, Handel TM (Feb 1999). "Solution structure and dynamics of the CX3C chemokine domain of fractalkine and its interaction with an N-terminal fragment of CX3CR1". Biochemistry 38 (5): 1402–14. doi:10.1021/bi9820614. PMID 9931005.
• Maho A, Bensimon A, Vassart G, Parmentier M (2000). "Mapping of the CCXCR1, CX3CR1, CCBP2 and CCR9 genes to the CCR cluster within the 3p21.3 region of the human genome". Cytogenetics and Cell Genetics 87 (3-4): 265–8. doi:10.1159/000015443. PMID 10702689.
• Faure S, Meyer L, Costagliola D, Vaneensberghe C, Genin E, Autran B, Delfraissy JF, McDermott DH, Murphy PM, Debré P, Théodorou I, Combadière C (Mar 2000). "Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1". Science 287 (5461): 2274–7. doi:10.1126/science.287.5461.2274. PMID 10731151.
• Yoneda O, Imai T, Goda S, Inoue H, Yamauchi A, Okazaki T, Imai H, Yoshie O, Bloom ET, Domae N, Umehara H (Apr 2000). "Fractalkine-mediated endothelial cell injury by NK cells". Journal of Immunology 164 (8): 4055–62. doi:10.4049/jimmunol.164.8.4055. PMID 10754298.
• Meucci O, Fatatis A, Simen AA, Miller RJ (Jul 2000). "Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival". Proceedings of the National Academy of Sciences of the United States of America 97 (14): 8075–80. doi:10.1073/pnas.090017497. PMC 16672. PMID 10869418.
• Papadopoulos EJ, Fitzhugh DJ, Tkaczyk C, Gilfillan AM, Sassetti C, Metcalfe DD, Hwang ST (Aug 2000). "Mast cells migrate, but do not degranulate, in response to fractalkine, a membrane-bound chemokine expressed constitutively in diverse cells of the skin". European Journal of Immunology 30 (8): 2355–61. doi:10.1002/1521-4141(2000)30:8<2355::AID-IMMU2355>3.0.CO;2-#. PMID 10940926.
• Moatti D, Faure S, Fumeron F, El Walid Amara M, Seknadji P, McDermott DH, Debré P, Aumont MC, Murphy PM, de Prost D, Combadière C (Apr 2001). "Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease". Blood 97 (7): 1925–8. doi:10.1182/blood.V97.7.1925. PMID 11264153.
• Foussat A, Bouchet-Delbos L, Berrebi D, Durand-Gasselin I, Coulomb-L'Hermine A, Krzysiek R, Galanaud P, Levy Y, Emilie D (Sep 2001). "Deregulation of the expression of the fractalkine/fractalkine receptor complex in HIV-1-infected patients". Blood 98 (6): 1678–86. doi:10.1182/blood.V98.6.1678. PMID 11535497.
• Dichmann S, Herouy Y, Purlis D, Rheinen H, Gebicke-Härter P, Norgauer J (Nov 2001). "Fractalkine induces chemotaxis and actin polymerization in human dendritic cells". Inflammation Research 50 (11): 529–33. doi:10.1007/PL00000230. PMID 11766992.
• Brand S, Sakaguchi T, Gu X, Colgan SP, Reinecker HC (Jan 2002). "Fractalkine-mediated signals regulate cell-survival and immune-modulatory responses in intestinal epithelial cells". Gastroenterology 122 (1): 166–77. doi:10.1053/gast.2002.30329. PMID 11781291.
• Utaipat U, Duerr A, Rudolph DL, Yang C, Butera ST, Lupo D, Pisell T, Tangmunkongvorakul A, Kamtorn N, Nantachit N, Nagachinta T, Suriyanon V, Robison V, Nelson KE, Sittisombut N, Lal RB (Jan 2002). "Coreceptor utilization of HIV type 1 subtype E viral isolates from Thai men with HIV type 1-infected and uninfected wives". AIDS Research and Human Retroviruses 18 (1): 1–11. doi:10.1089/088922202753394664. PMID 11804551.
• Fong AM, Alam SM, Imai T, Haribabu B, Patel DD (May 2002). "CX3CR1 tyrosine sulfation enhances fractalkine-induced cell adhesion". The Journal of Biological Chemistry 277 (22): 19418–23. doi:10.1074/jbc.M201396200. PMID 11909868.

External links

• CX3CR1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• "Chemokine Receptors: CX₃CR1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.