Fractalkine, also known as chemokine (C-X3-C motif) ligand 1, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the CX3CL1
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Function
Fractalkine is a large
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
protein of 373 amino acids, it contains multiple domains and is the only known member of the CX
3C
chemokine
Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additio ...
family. It is also commonly known under the names fractalkine (in humans) and neurotactin (in mice).
The polypeptide structure of CX3CL1 differs from the typical structure of other chemokines. For example, the spacing of the characteristic
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, sometime ...
s differs; there are three
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s 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
Mucins () are a family of high molecular weight, heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most ...
-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 cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
s and
monocyte
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...
s, while the cell-bound chemokine promotes strong adhesion of leukocytes to activated endothelial cells, where it is primarily expressed.
[ CX3CL1 elicits its adhesive and migratory functions by interacting with the chemokine receptor ]CX3CR1
CX3C motif chemokine receptor 1 (CX3CR1), also known as the fractalkine receptor or G-protein coupled receptor 13 (GPR13), is a transmembrane protein of the G protein-coupled receptor 1 (GPCR1) family and the only known member of the CX3C chemokin ...
. Its gene is located on human chromosome 16
Chromosome 16 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 16 spans about 90 million base pair
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting ...
along with some CC chemokines known as CCL17
CCL17 is a powerful chemokine produced in the thymus and by antigen-presenting cells like dendritic cells, macrophages, and monocytes. CCL17 plays a complex role in cancer. It attracts Regulatory T cell, T-regulatory cells allowing for some cance ...
and CCL22
C-C motif chemokine 22 is a protein that in humans is encoded by the ''CCL22'' gene.
The protein encoded by this gene is secreted by dendritic cells and macrophages, and elicits its effects on its target cells by interacting with cell surface che ...
.[
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.]hippocampus
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
during a brief temporal window following spatial learning
In cognitive psychology and neuroscience, spatial memory is a form of memory responsible for the recording and recovery of information needed to plan a course to a location and to recall the location of an object or the occurrence of an event. Sp ...
, 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
In neuroscience, synaptic scaling (or homeostatic scaling) is a form of homeostatic plasticity, in which the brain responds to chronically elevated activity in a neural circuit with negative feedback, allowing individual neurons to reduce their ove ...
.
References
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{{Chemokine receptor modulators
Cytokines