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 au ...

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 receptors, 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 (t ...

seven times. There are currently six known CXC chemokine receptors in mammals, named CXCR1 through CXCR6.

CXCR1 and CXCR2

CXCR1 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, 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 bind only CXCR2. They are both expressed on the surface of

neutrophils Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...

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 Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cell ...

cell types (e.g.

monocytes 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 ...

, T and B cells, dendritic cells,

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 the ...

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/

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 CX ...

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 (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 3p21) 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 Chemotaxis (from '' chemo-'' + '' taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemica ...

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.

References

External links

* {{Chemokine receptor modulators Chemokine receptors