CX3CR1

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.[5][6] As the name suggests, this receptor binds the chemokine CX3CL1 (also called neurotactin or fractalkine).

CX3CR1
Identifiers
Aliases	CX3CR1, CCRL1, CMKBRL1, CMKDR1, GPR13, GPRV28, V28, C-X3-C motif chemokine receptor 1
External IDs	OMIM: 601470 MGI: 1333815 HomoloGene: 20350 GeneCards: CX3CR1
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p22.2 Start 39,263,494 bp[1] End 39,281,735 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 F4 Start 119,901,616 bp[2] End 120,069,879 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • G-protein coupled receptor activity • C-X3-C chemokine receptor activity • signal transducer activity • GO:0001948 protein binding • chemokine receptor activity • C-X3-C chemokine binding • cytokine receptor activity • G-protein coupled peptide receptor activity • C-C chemokine receptor activity • chemokine binding • C-C chemokine binding Cellular component • integral component of membrane • membrane • cell membrane • integral component of plasma membrane • neuronal cell body membrane • perinuclear region of cytoplasm • neuron projection • cell nucleus • nucleoplasm • external side of plasma membrane • cell surface • dendritic tree Biological process • cellular response to transforming growth factor beta stimulus • positive regulation of neuroblast proliferation • G-protein coupled receptor signaling pathway • chemokine-mediated signaling pathway • memory • positive regulation of angiogenesis • chemotaxis • cellular defense response • cell adhesion • negative regulation of cell migration • response to wounding • negative regulation of long-term synaptic potentiation • GO:0022415 viral process • cellular response to lipopolysaccharide • signal transduction • microglial cell activation involved in immune response • negative regulation of angiogenesis • cytokine-mediated signaling pathway • cerebral cortex cell migration • macrophage chemotaxis • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand • response to ischemia • immune response • phospholipase C-activating G-protein coupled receptor signaling pathway • positive regulation of cytosolic calcium ion concentration • cell-cell signaling • calcium-mediated signaling • central nervous system maturation • negative regulation of interleukin-1 beta production • social organism behavior • autocrine signaling • regulation of tumor necrosis factor biosynthetic process • innate immune system • regulation of nitric oxide biosynthetic process • regulation of synaptic plasticity • regulation of neurogenesis • positive regulation of neurogenesis • modulation of chemical synaptic transmission • leukocyte tethering or rolling • positive regulation of NF-kappaB transcription factor activity • positive regulation of protein kinase B signaling • synapse maturation • cell chemotaxis • synapse disassembly • negative regulation of hippocampal neuron apoptotic process • multiple spine synapse organization, single dendrite • positive regulation of I-kappaB phosphorylation • regulation of microglial cell migration • negative regulation of apoptotic signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1524	13051
Ensembl	ENSG00000168329	ENSMUSG00000052336
UniProt	P49238	Q9Z0D9
RefSeq (mRNA)	NM_001337 NM_001171171 NM_001171172 NM_001171174	NM_009987
RefSeq (protein)	NP_001164642 NP_001164643 NP_001164645 NP_001328	NP_034117
Location (UCSC)	Chr 3: 39.26 – 39.28 Mb	Chr 9: 119.9 – 120.07 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The fractalkine ligand CX3CL1 is a transmembrane protein and chemokine involved in the adhesion and migration of leukocytes. The protein encoded by the CX3CR1 gene is a receptor for the fractalkine ligand.[7]

Expression of this receptor appears to be associated with lymphocytes.[8] CX3CR1 is also expressed by monocytes and plays a major role in the survival of monocytes.[9]

Fractalkine signaling 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 hippocampal neurons than wild-type mice.[10]

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.[7]

CX3CR1 variants have been described to modify the survival time and the progression rate of patients with amyotrophic lateral sclerosis.[11]

Mutations in CX3CR1 are associated to dysplasia of the hip.[12] Homozygous CX3CR1-M280 mutation impairs human monocyte survival and deteriorates outcome of human systemic candiasis.[13]

References

1. GRCh38: Ensembl release 89: ENSG00000168329 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000052336 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Combadiere C, Ahuja SK, Murphy PM (August 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.
6. Combadiere C, Salzwedel K, Smith ED, Tiffany HL, Berger EA, Murphy PM (September 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.
7. "Entrez Gene: chemokine (C-X3-C motif) receptor 1".
8. Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O (November 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.
9. Landsman L, Bar-On L, Zernecke A, Kim KW, Krauthgamer R, Shagdarsuren E, Lira SA, Weissman IL, Weber C, Jung S (January 2009). "CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival". Blood. 113 (4): 963–72. doi:10.1182/blood-2008-07-170787. PMID 18971423.
10. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, Giustetto M, Ferreira TA, Guiducci E, Dumas L, Ragozzino D, Gross CT (September 2011). "Synaptic pruning by microglia is necessary for normal brain development". Science. 333 (6048): 1456–8. doi:10.1126/science.1202529. PMID 21778362.
11. Lopez-Lopez A, Gamez J, Syriani E, Morales M, Salvado M, Rodríguez MJ, Mahy N, Vidal-Taboada JM (7 May 2014). "CX3CR1 is a modifying gene of survival and progression in amyotrophic lateral sclerosis". PLOS ONE. 9 (5): e96528. doi:10.1371/journal.pone.0096528. PMC 4013026. PMID 24806473.
12. Feldman GJ, Parvizi J, Sawan H, Erickson JA, Peters CL (September 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.
13. Collar AL, Swamydas M, O'Hayre M, Sajib MS, Hoffman KW, Singh SP, et al. (February 2018). "The homozygous CX3CR1-M280 mutation impairs human monocyte survival". JCI Insight. 3 (3). doi:10.1172/jci.insight.95417. PMC 5821174. PMID 29415879.

Further reading

• Robertson MJ (February 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 (October 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 (January 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 (October 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 (February 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 (March 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 (April 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 (July 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 (August 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, Amara M, Seknadji P, McDermott DH, Debré P, Aumont MC, Murphy PM, de Prost D, Combadière C (April 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 (September 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 (November 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 (January 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 (January 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.
• Human CX3CR1 genome location and CX3CR1 gene details page in the UCSC Genome Browser.

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