SDF-1 (
stromal cellIn cell biology, stromal cells are connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa , prostate, bone marrow precursor cells, and the ovary as well as the hematopoietic system and elsewhere...
-derived factor-1) is small
cytokineCytokines are any of a number of substances that are secreted by specific cells of the immune system which carry signals locally between cells, and thus have an effect on other cells. They are a category of signaling molecules that are used extensively in cellular communication. They are proteins,...
belonging to the
chemokineChemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
family that is officially designated
Chemokine (C-X-C motif) ligand 12 (CXCL12).
SDF-1 is produced in two forms, SDF-1α/CXCL12a and SDF-1β/CXCL12b, by alternate splicing of the same gene. Chemokines are characterized by the presence of four conserved
cysteineCysteine is an α-amino acid with the chemical formula HO
2CCHCH
2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is nonpolar and thus cysteine is usually classified as...
s, which form two disulfide bonds. The CXCL12 proteins belong to the group of CXC chemokines, whose initial pair of cysteines are separated by one intervening
amino acidAmino acids are molecules containing an amine group, a carboxylic acid group and one of the twenty R-groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H
2NCHRCOOH, where R is an organic substituent...
.
CXCL12 is strongly chemotactic for
lymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.By their appearance under the light microscope, there are two broad categories of lymphocytes, namely the large granular lymphocytes and the small lymphocytes. Functionally distinct subsets of lymphocytes correlate with...
s.
During embryogenesis it directs the migration of hematopoietic cells from foetal
liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
to
bone marrowBone marrow is the flexible tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells. It constitutes 4% of total body weight, i.e...
and the formation of large blood vessels.
SDF-1 (
stromal cellIn cell biology, stromal cells are connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa , prostate, bone marrow precursor cells, and the ovary as well as the hematopoietic system and elsewhere...
-derived factor-1) is small
cytokineCytokines are any of a number of substances that are secreted by specific cells of the immune system which carry signals locally between cells, and thus have an effect on other cells. They are a category of signaling molecules that are used extensively in cellular communication. They are proteins,...
belonging to the
chemokineChemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
family that is officially designated
Chemokine (C-X-C motif) ligand 12 (CXCL12).
Structure
SDF-1 is produced in two forms, SDF-1α/CXCL12a and SDF-1β/CXCL12b, by alternate splicing of the same gene. Chemokines are characterized by the presence of four conserved
cysteineCysteine is an α-amino acid with the chemical formula HO
2CCHCH
2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is nonpolar and thus cysteine is usually classified as...
s, which form two disulfide bonds. The CXCL12 proteins belong to the group of CXC chemokines, whose initial pair of cysteines are separated by one intervening
amino acidAmino acids are molecules containing an amine group, a carboxylic acid group and one of the twenty R-groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H
2NCHRCOOH, where R is an organic substituent...
.
Chemotaxis
CXCL12 is strongly chemotactic for
lymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.By their appearance under the light microscope, there are two broad categories of lymphocytes, namely the large granular lymphocytes and the small lymphocytes. Functionally distinct subsets of lymphocytes correlate with...
s.
During embryogenesis it directs the migration of hematopoietic cells from foetal
liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
to
bone marrowBone marrow is the flexible tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells. It constitutes 4% of total body weight, i.e...
and the formation of large blood vessels. Mice which were
knocked-outA gene knockout is a genetic technique in which an organism is engineered to carry genes that have been made inoperative . Also known as knockout organisms or simply knockouts, they are used in learning about a gene that has been sequenced, but which has an unknown or incompletely known function...
for CXCL12 gene were lethal before the birth or within just 1 hour of life.
In adulthood CXCL12 plays an important role in angiogenesis by recruiting endothelial progenitor cells (EPCs) from the bone morrow through a CXCR4 dependent mechanism. It is this function of CXCL12 that makes it a very important factor in carcinogenesis and the neovascularisation linked to tumour progression.
Others
CXCL12 was shown to be expressed in many tissues in mice (including
brainThe brain is the center of the nervous system in all vertebrate, and most invertebrate, animals. Some primitive animals such as jellyfish and starfish have a decentralized nervous system without a brain, while sponges lack any nervous system at all...
,
thymusIn human anatomy, the thymus is an organ located in the upper anterior portion of the chest cavity just behind the sternum. The main function of the thymus is to provide an area for T lymphocyte maturation, and is vital in protecting against autoimmunity....
,
heartThe heart is a muscular organ found in all vertebrates that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
,
lungThe lung or pulmonary system is the essential respiration organ in air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located in the chest on either side of the heart...
,
liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
,
kidneyThe kidneys are paired organs, which have the production of urine as their primary function. Kidneys are seen in many types of animals, including vertebrates and some invertebrates. They are part of the urinary system, but have several secondary functions concerned with homeostatic functions. ...
,
spleenThe spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells, holds a reserve in case of hemorrhagic shock, especially in...
and
bone marrowBone marrow is the flexible tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells. It constitutes 4% of total body weight, i.e...
).
Receptor
The
receptorChemokine receptors are cytokine receptors found on the surface of certain cells, which interact with a type of cytokine called a chemokine. There have been 19 distinct chemokine receptors described in mammals...
for this chemokine is CXCR4, which was previously called fusin. This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently it was suggested that CXCL12 may also bind the CXCR7 receptor.
Gene
The gene for CXCL12 is located on human chromosome 10. In human and mouse both CXCL12 and CXCR4 show high identity of sequence: 99% and 90%, respectively.
Further reading