, , , , , , | Name = Chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1) | HGNCid = 10672 | Symbol = CXCL12 | AltSymbols =; PBSF; SCYB12; SDF-1a; SDF-1b; SDF1; SDF1A; SDF1B; TLSF-a; TLSF-b; TPAR1 | OMIM = 600835 | ECnumber = | Homologene = 507 | MGIid = 103556 | GeneAtlas_image1 = PBB_GE_CXCL12_209687_at_tn.png | GeneAtlas_image2 = PBB_GE_CXCL12_203666_at_tn.png | Function = | Component = | Process = | Orthologs = }}

SDF-1 (stromal cell-derived factor-1) is small cytokine belonging to the chemokine family that is officially designated Chemokine (C-X-C motif) ligand 12 (CXCL12).

Structure

SDF-1 is produced in two forms, SDF-1?/CXCL12a and SDF-1?/CXCL12b, by alternate splicing of the same gene.De La Luz Sierra et al. Differential processing of stromal-derived factor-1alpha and beta explains functional diversity. Blood 103:2452-2459, 2004. Chemokines are characterized by the presence of four conserved cysteines, 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 acid.

Functions

Chemotaxis

CXCL12 is strongly chemotactic for lymphocytes.Bleul et al. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J. Exp. Med. 184: 1101-1109, 1996.Ara et al. Impaired colonization of the gonads by primordial germ cells in mice lacking a chemokine, stromal cell-derived factor-1 (SDF-1). Proc. Nat. Acad. Sci. 100: 5319-5323, 2003.Askari et al. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 362: 697-703, 2003.Ma et al. Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc. Nat. Acad. Sci. 95: 9448-9453, 1998.

During embryogenesis it directs the migration of hematopoietic cells from foetal liver to bone marrow and the formation of large blood vessels. Mice which were knocked-out for CXCL12 gene were lethal before the birth or within just 1 hour of life.
In adulthood CXCL12 plays an important role in angoigenesis by recruiting endothelial progenitor cells (EPC) from the bone morrow through a CXCR4 dependent mechanism.Zheng H, Fu G, Dai T, Huang H. Migration of endothelial progenitor cells mediated by stromal cell-derived factor-1alpha/CXCR4 via PI3K/Akt/eNOS signal transduction pathway.J Cardiovasc Pharmacol. 2007 Sep;50(3):274-80.Click here to read It is this function of CXCL12 that makes it a very important factor in carcinogenesis and the neovascularisation linked to tumour progression. Kryczek I, Wei S, Keller E, Liu R, Zou W. Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis. Am J Physiol Cell Physiol. 2007 Mar;292(3):C987-95.

Electrophysiology

As another role, CXCL12a alters also the electrophysiology of neurons.

Others

CXCL12 was shown to be expressend in many tissues in mice (including brain, thymus, heart, lung, liver, kidney, spleen and bone marrow).

Receptor

The receptor for this chemokine is CXCR4, which was previously called fusin.Bleul et al. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 382: 829-833, 1996. This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently it was suggested that CXCL12 is also bound by CXCR7 receptor.Balabanian et al. The chemokine SDF-1/CXCl12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J Biol Chem 280:35760-35766, 2005.Burns et al. A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med. 203:2201-2213, 2006.

Gene

The gene for CXCL12 is located on human chromosome 10.Deloukas et al. The DNA sequence and comparative analysis of human chromosome 10. Nature 429:375-381, 2004. In human and mouse both CXCL12 and CXCR4 show high identity of sequence: 99% and 90%, respectively.