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 can be classified as IMPs, but not all IMPs are transmembrane proteins. IMPs comp ...
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 produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
s of the
CXC chemokine 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-tran ...
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 or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
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
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 addit ...
, 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
Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in different ...
in mammals.
CXCR3
CXCR3 is expressed predominantly on
T cell
T cells (also known as T lymphocytes) are an important part 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 receptor (TCR) on their cell ...
s (T lymphocytes), and also on other lymphocytes
ome B cells (B lymphocytes) and NK cells">B_cell.html" ;"title="ome B cell">ome B cells (B lymphocytes) and NK cells] and 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
C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the ''CXCR4'' gene. The protein is a CXC chemokine receptor.
Function
CXCR-4 is an alpha- chemo ...
(also known as fusin) is the receptor for a chemokine known as
CXCL12 (or SDF-1) and, as with
CCR5
C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines.
In humans, the ''CCR5'' gene that encodes the CCR5 p ...
, 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 (; ; also hematopoiesis in American English, sometimes h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten ...
cell types (e.g.
neutrophils
Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in different ...
,
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 monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also i ...
, T and B cells,
dendritic cells
A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system ...
,
Langerhans cells
A Langerhans cell (LC) is a tissue-resident macrophage of the skin once thought to be a resident dendritic cell. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in ...
and
macrophages
Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
). In addition, CXCR4 can also be found on vascular endothelial cells and
neuronal
A neuron (American English), neurone (British English), or nerve cell, is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. They are located in the nervous system and help to ...
/
nerve cells
A neuron (American English), neurone (British English), or nerve cell, is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. They are located in the nervous system and help to ...
.
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 ...
is expressed on
B cells
B cells, also known as B lymphocytes, are a type 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 or inserted into the plasm ...
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, lymphoid organs, lympha ...
. Its principal ligand is
CXCL13 (or BLC).
CXCR6
CXCR6 was formerly called three different names (STRL33, BONZO, and TYMSTR) before being assigned
CXCR6 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 more than 201 million base pairs (the building material of DNA) and represents about 6.5 percent of the total DNA ...
p21) and its similarity to other chemokine receptors in its
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
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 ''chemical substance, chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell organism, single-cell or multicellular organisms direct thei ...
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