Fractalkine is a large cytokine protein of 373 amino acids, it contains multiple domains and is the only known member of the CX3C chemokine family. It is also commonly known under the names fractalkine (in humans) and neurotactin (in mice).[5][6] The polypeptide structure of CX3CL1 differs from the typical structure of other chemokines. For example, the spacing of the characteristic N-terminalcysteines differs; there are three amino acids separating the initial pair of cysteines in CX3CL1, with none in CC chemokines and only one intervening amino acid in CXC chemokines. CX3CL1 is produced as a long protein (with 373-amino acid in humans) with an extended mucin-like stalk and a chemokine domain on top. The mucin-like stalk permits it to bind to the surface of certain cells. However a soluble (90 kD) version of this chemokine has also been observed. Soluble CX3CL1 potently chemoattracts T cells and monocytes, while the cell-bound chemokine promotes strong adhesion of leukocytes to activated endothelial cells, where it is primarily expressed.[6] CX3CL1 elicits its adhesive and migratory functions by interacting with the chemokine receptor CX3CR1.[7] Its gene is located on human chromosome 16 along with some CC chemokines known as CCL17 and CCL22.[6][8]
Fractalkine is found commonly throughout the brain, particularly in neural cells, and its receptor is known to be present on microglial cells. It has also been found to be essential for microglial cell migration.[9] CX3CL1 is also up-regulated in the hippocampus during a brief temporal window following spatial learning, the purpose of which may be to regulate glutamate-mediated neurotransmission tone. This indicates a possible role for the chemokine in the protective plasticity process of synaptic scaling.[10]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000006210 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000031778 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Pan Y, Lloyd C, Zhou H, Dolich S, Deeds J, Gonzalo JA, Vath J, Gosselin M, Ma J, Dussault B, Woolf E, Alperin G, Culpepper J, Gutierrez-Ramos JC, Gearing D (1997). "Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation". Nature. 387 (6633): 611–617. Bibcode:1997Natur.387..611P. doi:10.1038/42491. PMID 9177350. S2CID 4307876.
^ abcBazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, Greaves DR, Zlotnik A, Schall TJ (1997). "A new class of membrane-bound chemokine with a CX3C motif". Nature. 385 (6617): 640–644. Bibcode:1997Natur.385..640B. doi:10.1038/385640a0. PMID 9024663. S2CID 4322166.
^Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O (1997). "Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion". Cell. 91 (4): 521–530. doi:10.1016/S0092-8674(00)80438-9. PMID 9390561. S2CID 17281691.
^Nomiyama H, Imai T, Kusuda J, Miura R, Callen DF, Yoshie O (1998). "Human chemokines fractalkine (SCYD1), MDC (SCYA22) and TARC (SCYA17) are clustered on chromosome 16q13". Cytogenet. Cell Genet. 81 (1): 10–11. doi:10.1159/000015000. PMID 9691168. S2CID 46851784.
^Maciejewski-Lenoir D, Chen S, Feng L, Maki R, Bacon KB (1999-08-01). "Characterization of fractalkine in rat brain cells: migratory and activation signals for CX3CR-1-expressing microglia". Journal of Immunology. 163 (3): 1628–1635. doi:10.4049/jimmunol.163.3.1628. ISSN 0022-1767. PMID 10415068.
^Sheridan GK, Wdowicz A, Pickering M, Watters O, Halley P, O'Sullivan NC, Mooney C, O'Connell DJ, O'Connor JJ, Murphy KJ (2014). "CX3CL1 is up-regulated in the rat hippocampus during memory-associated synaptic plasticity". Front Cell Neurosci. 8: 233. doi:10.3389/fncel.2014.00233. PMC4130185. PMID 25161610.
External linksedit
Human CX3CL1 genome location and CX3CL1 gene details page in the UCSC Genome Browser.
Further readingedit
Bazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, Greaves DR, Zlotnik A, Schall TJ (1997). "A new class of membrane-bound chemokine with a CX3C motif". Nature. 385 (6617): 640–4. Bibcode:1997Natur.385..640B. doi:10.1038/385640a0. PMID 9024663. S2CID 4322166.
Combadiere C, Salzwedel K, Smith ED, Tiffany HL, Berger EA, Murphy PM (1998). "Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1". J. Biol. Chem. 273 (37): 23799–804. doi:10.1074/jbc.273.37.23799. PMID 9726990.
Meucci O, Fatatis A, Simen AA, Bushell TJ, Gray PW, Miller RJ (1998). "Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity". Proc. Natl. Acad. Sci. U.S.A. 95 (24): 14500–5. Bibcode:1998PNAS...9514500M. doi:10.1073/pnas.95.24.14500. PMC24402. PMID 9826729.
Mizoue LS, Bazan JF, Johnson EC, Handel TM (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.
Papadopoulos EJ, Sassetti C, Saeki H, Yamada N, Kawamura T, Fitzhugh DJ, Saraf MA, Schall T, Blauvelt A, Rosen SD, Hwang ST (1999). "Fractalkine, a CX3C chemokine, is expressed by dendritic cells and is up-regulated upon dendritic cell maturation". Eur. J. Immunol. 29 (8): 2551–9. doi:10.1002/(SICI)1521-4141(199908)29:08<2551::AID-IMMU2551>3.0.CO;2-T. PMID 10458770.
Loftus BJ, Kim UJ, Sneddon VP, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD (1999). "Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q". Genomics. 60 (3): 295–308. doi:10.1006/geno.1999.5927. PMID 10493829.
Tong N, Perry SW, Zhang Q, James HJ, Guo H, Brooks A, Bal H, Kinnear SA, Fine S, Epstein LG, Dairaghi D, Schall TJ, Gendelman HE, Dewhurst S, Sharer LR, Gelbard HA (2000). "Neuronal fractalkine expression in HIV-1 encephalitis: roles for macrophage recruitment and neuroprotection in the central nervous system". J. Immunol. 164 (3): 1333–9. doi:10.4049/jimmunol.164.3.1333. PMID 10640747. S2CID 20616076.
Faure S, Meyer L, Costagliola D, Vaneensberghe C, Genin E, Autran B, Delfraissy JF, McDermott DH, Murphy PM, Debré P, Théodorou I, Combadière C (2000). "Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1". Science. 287 (5461): 2274–7. Bibcode:2000Sci...287.2274F. doi:10.1126/science.287.5461.2274. PMID 10731151.
Hoover DM, Mizoue LS, Handel TM, Lubkowski J (2000). "The crystal structure of the chemokine domain of fractalkine shows a novel quaternary arrangement". J. Biol. Chem. 275 (30): 23187–93. doi:10.1074/jbc.M002584200. PMID 10770945. S2CID 38835823.
Meucci O, Fatatis A, Simen AA, Miller RJ (2000). "Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival". Proc. Natl. Acad. Sci. U.S.A. 97 (14): 8075–80. Bibcode:2000PNAS...97.8075M. doi:10.1073/pnas.090017497. PMC16672. PMID 10869418.
Papadopoulos EJ, Fitzhugh DJ, Tkaczyk C, Gilfillan AM, Sassetti C, Metcalfe DD, Hwang ST (2000). "Mast cells migrate, but do not degranulate, in response to fractalkine, a membrane-bound chemokine expressed constitutively in diverse cells of the skin". Eur. J. Immunol. 30 (8): 2355–61. doi:10.1002/1521-4141(2000)30:8<2355::AID-IMMU2355>3.0.CO;2-#. PMID 10940926. S2CID 196597758.
Lucas AD, Chadwick N, Warren BF, Jewell DP, Gordon S, Powrie F, Greaves DR (2001). "The transmembrane form of the CX3CL1 chemokine fractalkine is expressed predominantly by epithelial cells in vivo". Am. J. Pathol. 158 (3): 855–66. doi:10.1016/S0002-9440(10)64034-5. PMC1850344. PMID 11238035.
Garton KJ, Gough PJ, Blobel CP, Murphy G, Greaves DR, Dempsey PJ, Raines EW (2001). "Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates the cleavage and shedding of fractalkine (CX3CL1)". J. Biol. Chem. 276 (41): 37993–8001. doi:10.1074/jbc.M106434200. PMID 11495925.
Umehara H, Bloom ET, Okazaki T, Nagano Y, Yoshie O, Imai T (2004). "Fractalkine in vascular biology: from basic research to clinical disease". Arterioscler. Thromb. Vasc. Biol. 24 (1): 34–40. doi:10.1161/01.ATV.0000095360.62479.1F. PMID 12969992. S2CID 6183022.
Umehara H, Tanaka M, Sawaki T, Jin ZX, Huang CR, Dong L, Kawanami T, Karasawa H, Masaki Y, Fukushima T, Hirose Y, Okazaki T (2006). "Fractalkine in rheumatoid arthritis and allied conditions". Mod Rheumatol. 16 (3): 124–30. doi:10.1007/s10165-006-0471-9. PMID 16767549. S2CID 10199059.
January 01, 1970
cx3cl1, fractalkine, also, known, chemokine, motif, ligand, protein, that, humans, encoded, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes1b2t, 1f2l, 3ona, 4xt1, 4xt3identifiersaliases, abcd, c3xkine, cxc3, cxc3c, scyd1, fractalkine, neu. Fractalkine also known as chemokine C X3 C motif ligand 1 is a protein that in humans is encoded by the CX3CL1 gene CX3CL1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes1B2T 1F2L 3ONA 4XT1 4XT3IdentifiersAliasesCX3CL1 ABCD 3 C3Xkine CXC3 CXC3C NTN NTT SCYD1 fractalkine neurotactin C X3 C motif chemokine ligand 1External IDsOMIM 601880 MGI 1097153 HomoloGene 2251 GeneCards CX3CL1Gene location Human Chr Chromosome 16 human 1 Band16q21Start57 372 477 bp 1 End57 385 044 bp 1 Gene location Mouse Chr Chromosome 8 mouse 2 Band8 C5 8 46 79 cMStart95 498 637 bp 2 End95 509 055 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inright lungright coronary arteryprefrontal cortexfrontal poleascending aortapopliteal arterydorsolateral prefrontal cortexlactiferous ductupper lobe of left lungBrodmann area 10Top expressed inentorhinal cortexvisual cortexolfactory tuberclesuperior frontal gyrusprimary motor cortexprefrontal cortexnucleus accumbensdentate gyrussubiculummedial dorsal nucleusMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functioncytokine activity chemokine activity protein binding CCR chemokine receptor binding signaling receptor binding integrin binding CX3C chemokine receptor bindingCellular componentintegral component of membrane membrane plasma membrane extracellular region cell surface extracellular spaceBiological processG protein coupled receptor signaling pathway defense response positive regulation of inflammatory response monocyte chemotaxis cytokine mediated signaling pathway chemokine mediated signaling pathway angiogenesis involved in wound healing cellular response to tumor necrosis factor wound healing leukocyte chemotaxis neutrophil chemotaxis positive regulation of angiogenesis positive regulation of transforming growth factor beta1 production positive regulation of GTPase activity cell adhesion immune response cellular response to interleukin 1 leukocyte adhesive activation positive regulation of ERK1 and ERK2 cascade cellular response to interferon gamma cell chemotaxis lymphocyte chemotaxis negative regulation of extrinsic apoptotic signaling pathway in absence of ligand positive regulation of calcium independent cell cell adhesion chemotaxis integrin activation negative regulation of cell migration leukocyte migration involved in inflammatory response macrophage chemotaxis regulation of signaling receptor activitySources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez637620312EnsemblENSG00000006210ENSMUSG00000031778UniProtP78423O35188RefSeq mRNA NM 002996NM 001304392NM 009142RefSeq protein NP 001291321NP 002987NP 033168Location UCSC Chr 16 57 37 57 39 MbChr 8 95 5 95 51 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 References 3 External links 4 Further readingFunction editFractalkine is a large cytokine protein of 373 amino acids it contains multiple domains and is the only known member of the CX3C chemokine family It is also commonly known under the names fractalkine in humans and neurotactin in mice 5 6 The polypeptide structure of CX3CL1 differs from the typical structure of other chemokines For example the spacing of the characteristic N terminal cysteines differs there are three amino acids separating the initial pair of cysteines in CX3CL1 with none in CC chemokines and only one intervening amino acid in CXC chemokines CX3CL1 is produced as a long protein with 373 amino acid in humans with an extended mucin like stalk and a chemokine domain on top The mucin like stalk permits it to bind to the surface of certain cells However a soluble 90 kD version of this chemokine has also been observed Soluble CX3CL1 potently chemoattracts T cells and monocytes while the cell bound chemokine promotes strong adhesion of leukocytes to activated endothelial cells where it is primarily expressed 6 CX3CL1 elicits its adhesive and migratory functions by interacting with the chemokine receptor CX3CR1 7 Its gene is located on human chromosome 16 along with some CC chemokines known as CCL17 and CCL22 6 8 Fractalkine is found commonly throughout the brain particularly in neural cells and its receptor is known to be present on microglial cells It has also been found to be essential for microglial cell migration 9 CX3CL1 is also up regulated in the hippocampus during a brief temporal window following spatial learning the purpose of which may be to regulate glutamate mediated neurotransmission tone This indicates a possible role for the chemokine in the protective plasticity process of synaptic scaling 10 References edit a b c GRCh38 Ensembl release 89 ENSG00000006210 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000031778 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Pan Y Lloyd C Zhou H Dolich S Deeds J Gonzalo JA Vath J Gosselin M Ma J Dussault B Woolf E Alperin G Culpepper J Gutierrez Ramos JC Gearing D 1997 Neurotactin a membrane anchored chemokine upregulated in brain inflammation Nature 387 6633 611 617 Bibcode 1997Natur 387 611P doi 10 1038 42491 PMID 9177350 S2CID 4307876 a b c Bazan JF Bacon KB Hardiman G Wang W Soo K Rossi D Greaves DR Zlotnik A Schall TJ 1997 A new class of membrane bound chemokine with a CX3C motif Nature 385 6617 640 644 Bibcode 1997Natur 385 640B doi 10 1038 385640a0 PMID 9024663 S2CID 4322166 Imai T Hieshima K Haskell C Baba M Nagira M Nishimura M Kakizaki M Takagi S Nomiyama H Schall TJ Yoshie O 1997 Identification and molecular characterization of fractalkine receptor CX3CR1 which mediates both leukocyte migration and adhesion Cell 91 4 521 530 doi 10 1016 S0092 8674 00 80438 9 PMID 9390561 S2CID 17281691 Nomiyama H Imai T Kusuda J Miura R Callen DF Yoshie O 1998 Human chemokines fractalkine SCYD1 MDC SCYA22 and TARC SCYA17 are clustered on chromosome 16q13 Cytogenet Cell Genet 81 1 10 11 doi 10 1159 000015000 PMID 9691168 S2CID 46851784 Maciejewski Lenoir D Chen S Feng L Maki R Bacon KB 1999 08 01 Characterization of fractalkine in rat brain cells migratory and activation signals for CX3CR 1 expressing microglia Journal of Immunology 163 3 1628 1635 doi 10 4049 jimmunol 163 3 1628 ISSN 0022 1767 PMID 10415068 Sheridan GK Wdowicz A Pickering M Watters O Halley P O Sullivan NC Mooney C O Connell DJ O Connor JJ Murphy KJ 2014 CX3CL1 is up regulated in the rat hippocampus during memory associated synaptic plasticity Front Cell Neurosci 8 233 doi 10 3389 fncel 2014 00233 PMC 4130185 PMID 25161610 External links editHuman CX3CL1 genome location and CX3CL1 gene details page in the UCSC Genome Browser Further reading editBazan JF Bacon KB Hardiman G Wang W Soo K Rossi D Greaves DR Zlotnik A Schall TJ 1997 A new class of membrane bound chemokine with a CX3C motif Nature 385 6617 640 4 Bibcode 1997Natur 385 640B doi 10 1038 385640a0 PMID 9024663 S2CID 4322166 Combadiere C Salzwedel K Smith ED Tiffany HL Berger EA Murphy PM 1998 Identification of CX3CR1 A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV 1 J Biol Chem 273 37 23799 804 doi 10 1074 jbc 273 37 23799 PMID 9726990 Meucci O Fatatis A Simen AA Bushell TJ Gray PW Miller RJ 1998 Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity Proc Natl Acad Sci U S A 95 24 14500 5 Bibcode 1998PNAS 9514500M doi 10 1073 pnas 95 24 14500 PMC 24402 PMID 9826729 Mizoue LS Bazan JF Johnson EC Handel TM 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 Papadopoulos EJ Sassetti C Saeki H Yamada N Kawamura T Fitzhugh DJ Saraf MA Schall T Blauvelt A Rosen SD Hwang ST 1999 Fractalkine a CX3C chemokine is expressed by dendritic cells and is up regulated upon dendritic cell maturation Eur J Immunol 29 8 2551 9 doi 10 1002 SICI 1521 4141 199908 29 08 lt 2551 AID IMMU2551 gt 3 0 CO 2 T PMID 10458770 Loftus BJ Kim UJ Sneddon VP Kalush F Brandon R Fuhrmann J Mason T Crosby ML Barnstead M Cronin L Deslattes Mays A Cao Y Xu RX Kang HL Mitchell S Eichler EE Harris PC Venter JC Adams MD 1999 Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q Genomics 60 3 295 308 doi 10 1006 geno 1999 5927 PMID 10493829 Tong N Perry SW Zhang Q James HJ Guo H Brooks A Bal H Kinnear SA Fine S Epstein LG Dairaghi D Schall TJ Gendelman HE Dewhurst S Sharer LR Gelbard HA 2000 Neuronal fractalkine expression in HIV 1 encephalitis roles for macrophage recruitment and neuroprotection in the central nervous system J Immunol 164 3 1333 9 doi 10 4049 jimmunol 164 3 1333 PMID 10640747 S2CID 20616076 Faure S Meyer L Costagliola D Vaneensberghe C Genin E Autran B Delfraissy JF McDermott DH Murphy PM Debre P Theodorou I Combadiere C 2000 Rapid progression to AIDS in HIV individuals with a structural variant of the chemokine receptor CX3CR1 Science 287 5461 2274 7 Bibcode 2000Sci 287 2274F doi 10 1126 science 287 5461 2274 PMID 10731151 Hoover DM Mizoue LS Handel TM Lubkowski J 2000 The crystal structure of the chemokine domain of fractalkine shows a novel quaternary arrangement J Biol Chem 275 30 23187 93 doi 10 1074 jbc M002584200 PMID 10770945 S2CID 38835823 Meucci O Fatatis A Simen AA Miller RJ 2000 Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival Proc Natl Acad Sci U S A 97 14 8075 80 Bibcode 2000PNAS 97 8075M doi 10 1073 pnas 090017497 PMC 16672 PMID 10869418 Papadopoulos EJ Fitzhugh DJ Tkaczyk C Gilfillan AM Sassetti C Metcalfe DD Hwang ST 2000 Mast cells migrate but do not degranulate in response to fractalkine a membrane bound chemokine expressed constitutively in diverse cells of the skin Eur J Immunol 30 8 2355 61 doi 10 1002 1521 4141 2000 30 8 lt 2355 AID IMMU2355 gt 3 0 CO 2 PMID 10940926 S2CID 196597758 Lucas AD Chadwick N Warren BF Jewell DP Gordon S Powrie F Greaves DR 2001 The transmembrane form of the CX3CL1 chemokine fractalkine is expressed predominantly by epithelial cells in vivo Am J Pathol 158 3 855 66 doi 10 1016 S0002 9440 10 64034 5 PMC 1850344 PMID 11238035 Garton KJ Gough PJ Blobel CP Murphy G Greaves DR Dempsey PJ Raines EW 2001 Tumor necrosis factor alpha converting enzyme ADAM17 mediates the cleavage and shedding of fractalkine CX3CL1 J Biol Chem 276 41 37993 8001 doi 10 1074 jbc M106434200 PMID 11495925 Umehara H Bloom ET Okazaki T Nagano Y Yoshie O Imai T 2004 Fractalkine in vascular biology from basic research to clinical disease Arterioscler Thromb Vasc Biol 24 1 34 40 doi 10 1161 01 ATV 0000095360 62479 1F PMID 12969992 S2CID 6183022 Umehara H Tanaka M Sawaki T Jin ZX Huang CR Dong L Kawanami T Karasawa H Masaki Y Fukushima T Hirose Y Okazaki T 2006 Fractalkine in rheumatoid arthritis and allied conditions Mod Rheumatol 16 3 124 30 doi 10 1007 s10165 006 0471 9 PMID 16767549 S2CID 10199059 Retrieved from https en wikipedia org w index php title CX3CL1 amp oldid 1191693811, wikipedia, wiki, book, books, library,
