Biology:CX3CL1
Generic protein structure example |
Fractalkine, also known as chemokine (C-X3-C motif) ligand 1, is a protein that in humans is encoded by the CX3CL1 gene.
Function
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).[1][2] 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.[2] CX3CL1 elicits its adhesive and migratory functions by interacting with the chemokine receptor CX3CR1.[3] Its gene is located on human chromosome 16 along with some CC chemokines known as CCL17 and CCL22.[2][4]
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.[5] 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.[6]
References
- ↑ "Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation". Nature 387 (6633): 611–617. 1997. doi:10.1038/42491. PMID 9177350. Bibcode: 1997Natur.387..611P.
- ↑ 2.0 2.1 2.2 "A new class of membrane-bound chemokine with a CX3C motif". Nature 385 (6617): 640–644. 1997. doi:10.1038/385640a0. PMID 9024663. Bibcode: 1997Natur.385..640B.
- ↑ "Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion". Cell 91 (4): 521–530. 1997. doi:10.1016/S0092-8674(00)80438-9. PMID 9390561.
- ↑ "Human chemokines fractalkine (SCYD1), MDC (SCYA22) and TARC (SCYA17) are clustered on chromosome 16q13". Cytogenet. Cell Genet. 81 (1): 10–11. 1998. doi:10.1159/000015000. PMID 9691168.
- ↑ Maciejewski-Lenoir, D.; Chen, S.; Feng, L.; Maki, R.; Bacon, K. B. (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.
- ↑ "CX3CL1 is up-regulated in the rat hippocampus during memory-associated synaptic plasticity". Front Cell Neurosci 8: 233. 2014. doi:10.3389/fncel.2014.00233. PMID 25161610.
External links
- Human CX3CL1 genome location and CX3CL1 gene details page in the UCSC Genome Browser.
Further reading
- "A new class of membrane-bound chemokine with a CX3C motif". Nature 385 (6617): 640–4. 1997. doi:10.1038/385640a0. PMID 9024663. Bibcode: 1997Natur.385..640B.
- "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. 1998. doi:10.1074/jbc.273.37.23799. PMID 9726990.
- "Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity". Proc. Natl. Acad. Sci. U.S.A. 95 (24): 14500–5. 1998. doi:10.1073/pnas.95.24.14500. PMID 9826729. Bibcode: 1998PNAS...9514500M.
- "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. 1999. doi:10.1021/bi9820614. PMID 9931005.
- "Fractalkine, a CX3C chemokine, is expressed by dendritic cells and is up-regulated upon dendritic cell maturation". Eur. J. Immunol. 29 (8): 2551–9. 1999. doi:10.1002/(SICI)1521-4141(199908)29:08<2551::AID-IMMU2551>3.0.CO;2-T. PMID 10458770.
- "Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q". Genomics 60 (3): 295–308. 1999. doi:10.1006/geno.1999.5927. PMID 10493829.
- "Neuronal fractalkine expression in HIV-1 encephalitis: roles for macrophage recruitment and neuroprotection in the central nervous system". J. Immunol. 164 (3): 1333–9. 2000. doi:10.4049/jimmunol.164.3.1333. PMID 10640747.
- "Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1". Science 287 (5461): 2274–7. 2000. doi:10.1126/science.287.5461.2274. PMID 10731151. Bibcode: 2000Sci...287.2274F.
- "The crystal structure of the chemokine domain of fractalkine shows a novel quaternary arrangement". J. Biol. Chem. 275 (30): 23187–93. 2000. doi:10.1074/jbc.M002584200. PMID 10770945.
- "Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival". Proc. Natl. Acad. Sci. U.S.A. 97 (14): 8075–80. 2000. doi:10.1073/pnas.090017497. PMID 10869418. Bibcode: 2000PNAS...97.8075M.
- "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. 2000. doi:10.1002/1521-4141(2000)30:8<2355::AID-IMMU2355>3.0.CO;2-#. PMID 10940926.
- "The transmembrane form of the CX3CL1 chemokine fractalkine is expressed predominantly by epithelial cells in vivo". Am. J. Pathol. 158 (3): 855–66. 2001. doi:10.1016/S0002-9440(10)64034-5. PMID 11238035.
- "Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates the cleavage and shedding of fractalkine (CX3CL1)". J. Biol. Chem. 276 (41): 37993–8001. 2001. doi:10.1074/jbc.M106434200. PMID 11495925.
- "Fractalkine in vascular biology: from basic research to clinical disease". Arterioscler. Thromb. Vasc. Biol. 24 (1): 34–40. 2004. doi:10.1161/01.ATV.0000095360.62479.1F. PMID 12969992.
- "Fractalkine in rheumatoid arthritis and allied conditions". Mod Rheumatol 16 (3): 124–30. 2006. doi:10.1007/s10165-006-0471-9. PMID 16767549.
Original source: https://en.wikipedia.org/wiki/CX3CL1.
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