Fractalkine, also known as chemokine (C-X3-C motif) ligand 1, is a protein that in humans is encoded by the CX3CL1 gene.

CX3CL1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCX3CL1, ABCD-3, C3Xkine, CXC3, CXC3C, NTN, NTT, SCYD1, fractalkine, neurotactin, C-X3-C motif chemokine ligand 1
External IDsOMIM: 601880; MGI: 1097153; HomoloGene: 2251; GeneCards: CX3CL1; OMA:CX3CL1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002996
NM_001304392

NM_009142

RefSeq (protein)

NP_001291321
NP_002987

NP_033168

Location (UCSC)Chr 16: 57.37 – 57.39 MbChr 8: 95.5 – 95.51 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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Fractalkine is a large cytokine protein of 373 amino acids that 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

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000006210Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031778Ensembl, 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. ^ 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.
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
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Further reading

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