View source for CX3CR1

{{Infobox_gene}}
'''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]].<ref name="pmid7646814">{{cite journal | vauthors = Combadiere C, Ahuja SK, Murphy PM | title = Cloning, chromosomal localization, and RNA expression of a human beta chemokine receptor-like gene | journal = DNA and Cell Biology | volume = 14 | issue = 8 | pages = 673–80 | date = August 1995 | pmid = 7646814 | doi = 10.1089/dna.1995.14.673 }}</ref><ref name="pmid9726990">{{cite journal | vauthors = Combadiere C, Salzwedel K, Smith ED, Tiffany HL, Berger EA, Murphy PM | title = Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 37 | pages = 23799–804 | date = September 1998 | pmid = 9726990 | doi = 10.1074/jbc.273.37.23799 }}</ref>  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 [[cell adhesion|adhesion]] and [[cell migration|migration]] of [[leukocyte]]s. The protein encoded by the CX3CR1 gene is a receptor for the fractalkine ligand.<ref name="entrez">{{cite web | title = Entrez Gene: chemokine (C-X3-C motif) receptor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1524| accessdate = }}</ref>

Expression of this receptor appears to be associated with [[lymphocytes]].<ref name="pmid9390561">{{cite journal | vauthors = Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O | title = Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion | journal = Cell | volume = 91 | issue = 4 | pages = 521–30 | date = November 1997 | pmid = 9390561 | doi = 10.1016/S0092-8674(00)80438-9 }}</ref> CX3CR1 is also expressed by monocytes and plays a major role in the survival of monocytes.<ref>{{cite journal | vauthors = Landsman L, Bar-On L, Zernecke A, Kim KW, Krauthgamer R, Shagdarsuren E, Lira SA, Weissman IL, Weber C, Jung S | title = CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival | journal = Blood | volume = 113 | issue = 4 | pages = 963–72 | date = January 2009 | pmid = 18971423 | doi = 10.1182/blood-2008-07-170787 }}</ref>

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 cortical neurons than wild-type mice.<ref>{{cite journal | vauthors = Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, Giustetto M, Ferreira TA, Guiducci E, Dumas L, Ragozzino D, Gross CT | title = Synaptic pruning by microglia is necessary for normal brain development | language = en | journal = Science | volume = 333 | issue = 6048 | pages = 1456–8 | date = September 2011 | pmid = 21778362 | doi = 10.1126/science.1202529 }}</ref>

== Clinical significance ==

CX3CR1 also is a coreceptor for HIV-1, and some variations in this gene lead to increased susceptibility to [[Subtypes of HIV#HIV-1|HIV-1]] infection and rapid progression to [[AIDS]].<ref name="entrez"/>

CX3CR1 variants have been described to modify the survival time and the progression rate of patients with [[amyotrophic lateral sclerosis]].<ref>{{cite journal | vauthors = Lopez-Lopez A, Gamez J, Syriani E, Morales M, Salvado M, Rodríguez MJ, Mahy N, Vidal-Taboada JM | title = CX3CR1 is a modifying gene of survival and progression in amyotrophic lateral sclerosis | journal = PLOS One | volume = 9 | issue = 5 | pages = e96528 | date = 7 May 2014 | pmid = 24806473 | pmc = 4013026 | doi = 10.1371/journal.pone.0096528 }}</ref>

Mutations in CX3CR1 are associated to {{SWL|type=mutations_associated_to|target=dysplasia of the hip|label=dysplasia of the hip}}.<ref>{{cite journal | vauthors = Feldman GJ, Parvizi J, Sawan H, Erickson JA, Peters CL | title = Linkage mapping and whole exome sequencing identify a shared variant in CX3CR1 in a large multi-generation family | journal = The Journal of Arthroplasty | volume = 29 | issue = 9 Suppl | pages = 238–41 | date = September 2014 | pmid = 24998320 | doi = 10.1016/j.arth.2014.05.014 }}</ref>
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== References ==
{{Reflist|33em}}

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

== External links ==
* {{MeshName|CX3CR1+protein,+human}}
* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2242 | title = Chemokine Receptors: CX<sub>3</sub>CR1 | accessdate = | authorlink = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | archiveurl = | archivedate = | quote = }}
* {{UCSC gene info|CX3CR1}}

{{NLM content}}
{{Chemokine receptors}}
{{Chemokine receptor modulators}}

[[Category:Cytokines]]
[[Category:Cell biology]]
[[Category:Receptors]]
[[Category:Integral membrane proteins]]