User:Ackeralexa/CXCR4

Function

[edit] CXCR-4 is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes. CXCR4 is one of several chemokine co-receptors that HIV can use to infect CD4+ T cells. HIV isolates that use CXCR4 are traditionally known as T-cell tropic isolates. Typically, these viruses are found late in infection. It is unclear as to whether the emergence of CXCR4-using HIV is a consequence or a cause of immunodeficiency.^{[citation needed]}

CXCR4 is upregulated during the implantation window in natural and hormone replacement therapy cycles in the endometrium, producing, in presence of a human blastocyst, a surface polarization of the CXCR4 receptors suggesting that this receptor is implicated in the adhesion phase of human implantation.^{[citation needed]}

CXCR4's ligand SDF-1 is known to be important in hematopoietic stem cell homing to the bone marrow and in hematopoietic stem cell quiescence. It has been also shown that CXCR4 signalling regulates the expression of CD20 on B cells. Until recently, SDF-1 and CXCR4 were believed to be a relatively monogamous ligand-receptor pair (other chemokines are promiscuous, tending to use several different chemokine receptors). Recent evidence demonstrates ubiquitin is also a natural ligand of CXCR4. Ubiquitin is a small (76-amino acid) protein highly conserved among eukaryotic cells. It is best known for its intracellular role in targeting ubiquitylated proteins for degradation via the ubiquitin proteasome system. Evidence in numerous animal models suggests ubiquitin is anti-inflammatory immune modulator and endogenous opponent of proinflammatory damage associated molecular pattern molecules. It is speculated this interaction may be through CXCR4 mediated signalling pathways. MIF is an additional ligand of CXCR4.

CXCR4 is present in newly generated neurons during both embryogenesis and adult life, where it plays a crucial role in neuronal guidance. In response to neural injury, such as ischemic stroke, the levels of SDF-1 are upregulated by astrocytes and endothelial cells. The up-regulation of SDF-1α forms a chemokine gradient that acts as a directional cue to guide neuroblasts. As neuroblasts move along this gradient, SDF-1 binds to CXCR4, activating pathways essential for NSC proliferation, survival, and directed migration (P13K/Akt, MAPK, and JAK2/STAT). These pathways promote the ability of neuroblasts to move towards the source of SDF-1, both increasing the number and density of chains and guiding them in a coordinated direction. However, as neurons mature, the expression of CXCR4 decrease. In CXCR4 mutant mice, abnormal neuronal distribution occurs, which has been implicated in disorders such as epilepsy.

CXCR4 dimerization is dynamic and increases with concentration.