CXC chemokine receptors are
integral membrane protein
An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a sign ...
s that specifically bind and respond to
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 ...
s of the
CXC 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. They represent one subfamily of
chemokine receptor
Chemokine receptors are cytokine receptors found on the surface of certain cells that interact with a type of cytokine called a chemokine. There have been 20 distinct chemokine receptors discovered in humans. Each has a rhodopsin-like 7-trans ...
s, a large family of
G protein-linked receptors that are known as seven transmembrane (7-TM) proteins, since they span the
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
seven times. There are currently six known CXC chemokine receptors in mammals, named CXCR1 through CXCR6.
CXCR1 and CXCR2
CXCR1
Interleukin 8 receptor, alpha is a chemokine receptor. This name and the corresponding gene symbol IL8RA have been replaced by the HGNC approved name C-X-C motif chemokine receptor 1 and the approved symbol CXCR1. It has also been designated as CD ...
and
CXCR2 are closely related receptors that recognize CXC chemokines that possess an E-L-R amino acid motif immediately adjacent to their CXC motif. CXCL8 (otherwise known as
interleukin-8
Interleukin 8 (IL-8 or chemokine (C-X-C motif) ligand 8, CXCL8) is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage ...
) and
CXCL6 can both bind CXCR1 in humans, while all other ELR-positive
chemokines
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 addition ...
, such as
CXCL1
The chemokine (C-X-C motif) ligand 1 (CXCL1) is a small peptide belonging to the CXC chemokine family that acts as a chemoattractant for several immune cells, especially neutrophils or other non-hematopoietic cells to the site of injury or infecti ...
to
CXCL7
Chemokine (C-X-C motif) ligand 7 (CXCL7) is a human gene.
The encoded protein, Chemokine (C-X-C motif) ligand is a small cytokine belonging to the CXC chemokine family. It is an isoform of Beta-Thromboglobulin or ''Pro-Platelet basic protein'' ( ...
bind only CXCR2.
They are both expressed on the surface of
neutrophils in mammals.
CXCR3
CXCR3
Chemokine receptor CXCR3 is a Gαi protein-coupled receptor in the CXC chemokine receptor family. Other names for CXCR3 are G protein-coupled receptor 9 (GPR9) and CD183. There are three isoforms of CXCR3 in humans: CXCR3-A, CXCR3-B and chemokin ...
is expressed predominantly on
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 (T lymphocytes), and also on other lymphocytes
ome_B_cells_(B_lymphocytes)_and_
ome_B_cells_(B_lymphocytes)_and_NK_cells">B_cell.html"_;"title="ome_B_cell">ome_B_cells_(B_lymphocytes)_and_NK_cells.html" ;"title="NK_cells.html" ;"title="B_cell.html" ;"title="ome B cell">ome B cells (B lymphocytes) and NK cells">B_cell.html" ;"title="ome B cell">ome B cells (B lymphocytes) and NK cells">NK_cells.html" ;"title="B_cell.html" ;"title="ome B cell">ome B cells (B lymphocytes) and NK cells">B_cell.html" ;"title="ome B cell">ome B cells (B lymphocytes) and NK cellsand is highly induced following cell activation. There are two isoforms, CXCR3-A and CXCR3-B.
It has three highly related ligands in mammals, CXCL9, CXCL10 and CXCL11.
CXCR4
CXCR4 (also known as fusin) is the receptor for a chemokine known as CXCL12 (or SDF-1) and, as with CCR5, is utilized by HIV-1 to gain entry into target cells. This receptor has a wide cellular distribution, with expression on most immature and mature
hematopoietic cell types (e.g.
neutrophils,
monocytes, T and B cells,
dendritic cells
Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. The ...
,
Langerhans cells
A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in t ...
and
macrophages
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
). In addition, CXCR4 can also be found on vascular endothelial cells and
neuronal
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. No ...
/
nerve cells
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...
.
CXCR5
The chemokine receptor
CXCR5
C-X-C chemokine receptor type 5 (CXC-R5) also known as CD185 (cluster of differentiation 185) or Burkitt lymphoma receptor 1 (BLR1) is a G protein-coupled seven transmembrane receptor for chemokine CXCL13 (also known as BLC) and belongs to the C ...
is expressed on
B cells
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...
and CD4+ Tfh cells and is involved in
lymphocyte homing and the development of normal
lymphoid tissue
The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid o ...
. Its principal ligand is
CXCL13
Chemokine (C-X-C motif) ligand 13 (CXCL13), also known as B lymphocyte chemoattractant (BLC) or B cell-attracting chemokine 1 (BCA-1), is a protein ligand that in humans is encoded by the ''CXCL13'' gene.
Function
CXCL13 is a small chemokine ...
(or BLC).
CXCR6
CXCR6 was formerly called three different names (STRL33, BONZO, and TYMSTR) before being assigned
CXCR6
C-X-C chemokine receptor type 6 is a protein that in humans is encoded by the ''CXCR6'' gene. CXCR6 has also recently been designated CD186 (cluster of differentiation
The cluster of differentiation (also known as cluster of designation or classi ...
based on its chromosomal location (within the chemokine receptor cluster on human
chromosome 3
Chromosome 3 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 3 spans almost 200 million base pairs (the building material of DNA) and represents about 6.5 percent of the total DNA in ...
p21) and its similarity to other chemokine receptors in its
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 b ...
sequence. CXCR6 binds the ligand
CXCL16. However, CXCR6 is more closely related in structure to CC chemokine receptors than to other CXC chemokine receptors.
History
ACKR3 was originally called RDC-1 (an orphan receptor) but has since been shown to cause
chemotaxis in T lymphocytes in response to CXCL12 (the ligand for CXCR4) prompting the renaming of this molecule as CXCR7.
ACKR3 designation has been accepted by the IUIS/WHO Subcommittee on Chemokine Nomenclature.
This receptor has also been identified on
memory B cells
In immunology, a memory B cell (MBC) is a type of B lymphocyte that forms part of the adaptive immune system. These cells develop within germinal centers of the secondary lymphoid organs. Memory B cells circulate in the blood stream in a quiesce ...
.
References
External links
*
{{Chemokine receptor modulators
Chemokine receptors