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Gene Review

Cxcr4  -  chemokine (C-X-C motif) receptor 4

Rattus norvegicus

Synonyms: C-X-C chemokine receptor type 4, CXC-R4, CXCR-4, Cmkar4, Fusin, ...
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Disease relevance of Cxcr4

  • Neurons were stimulated with the HIV envelope protein gp120(IIIB) or the endogenous CXCR 4 agonist, SDF-1 alpha [1].
  • DEX pretreatment decreased CXCR4 receptor density in the penumbra and attenuated astrocytosis [2].
  • Dexamethasone downregulates chemokine receptor CXCR4 and exerts neuroprotection against hypoxia/ischemia-induced brain injury in neonatal rats [2].
  • The compound exhibits potent inhibitory activity against a panel of R5-(virus using the CCR5 coreceptor), X4-(virus using the CXCR4 coreceptor), and R5/X4 HIV-1 laboratory and clinical isolates of the B subtype (median EC50 of 0.04 microM) in culture assays [3].
  • Both T140, a CXCR4 antagonist, and pertussis toxin (PTX), an inactivator of G protein-coupled receptors, abrogated these events [4].

Psychiatry related information on Cxcr4


High impact information on Cxcr4

  • The chemokine SDF-1/CXCL12 modulates the firing pattern of vasopressin neurons and counteracts induced vasopressin release through CXCR4 [6].
  • Expression of stromal cell-derived factor-1 and of its receptor CXCR4 in liver regeneration from oval cells in rat [7].
  • At the early stages, from day 2 to day 4 in culture, CXCR4 is particularly concentrated at the leading edge of growing neurites [8].
  • In conclusion, we demonstrate that SDF1alpha causes both proliferation and growth hormone release from pituitary adenoma cells, suggesting that the activation of CXCR4 may represent a novel regulatory mechanism for growth hormone secretion and pituitary cell proliferation, which may contribute to pituitary adenoma development [9].
  • Thus, the stimulation of different p53 targets could be instrumental in determining the outcome of CXCR 4 activation on neuronal survival in neuro-inflammatory disorders [1].

Chemical compound and disease context of Cxcr4


Biological context of Cxcr4


Anatomical context of Cxcr4


Associations of Cxcr4 with chemical compounds


Physical interactions of Cxcr4

  • CONCLUSION: The rapid enhancement in CXCR4 chemokine receptor binding in the affected brain areas suggests that SDF-1 alpha/CXCR4 may play a role in the hypoxia-induced inflammatory reaction in the neonatal brain [2].

Other interactions of Cxcr4


Analytical, diagnostic and therapeutic context of Cxcr4

  • In order to better understand the role of SDF-1 in the development of central neurons, we studied the cellular distribution of the SDF-1 receptor CXCR4 by immunocytochemistry of developing hippocampal neurons and tested the effect of SDF-1 in process patterning at the early stages of neuronal development [8].
  • Using confocal microscopy, a differential distribution of CXCR4 in neuronal perikarya and dendrites can be observed according to the brain structure [5].
  • The density of CXCR4 receptors was determined by quantitative autoradiography using [(125)I]SDF-1 alpha as a ligand [2].
  • By using RT-PCR, immunoblot analysis, and immunofluorescence microscopy, we first showed expression of both CXCR4 and its ligand by IEC-6 cells [16].
  • Sequence analysis and infectious recombinant viruses containing peripheral nerve-derived C2V3 sequences indicated a predominance of CCR5-dependent and macrophage-tropic HIV-1, although dual tropic viruses using both CCR5 and CXCR4 were identified [17].


  1. Regulation of neuronal P53 activity by CXCR 4. Khan, M.Z., Shimizu, S., Patel, J.P., Nelson, A., Le, M.T., Mullen-Przeworski, A., Brandimarti, R., Fatatis, A., Meucci, O. Mol. Cell. Neurosci. (2005) [Pubmed]
  2. Dexamethasone downregulates chemokine receptor CXCR4 and exerts neuroprotection against hypoxia/ischemia-induced brain injury in neonatal rats. Felszeghy, K., Banisadr, G., Rostène, W., Nyakas, C., Haour, F. Neuroimmunomodulation (2004) [Pubmed]
  3. A small molecule HIV-1 inhibitor that targets the HIV-1 envelope and inhibits CD4 receptor binding. Lin, P.F., Blair, W., Wang, T., Spicer, T., Guo, Q., Zhou, N., Gong, Y.F., Wang, H.G., Rose, R., Yamanaka, G., Robinson, B., Li, C.B., Fridell, R., Deminie, C., Demers, G., Yang, Z., Zadjura, L., Meanwell, N., Colonno, R. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  4. Stromal cell-derived factor 1-mediated CXCR4 signaling in rat and human cortical neural progenitor cells. Peng, H., Huang, Y., Rose, J., Erichsen, D., Herek, S., Fujii, N., Tamamura, H., Zheng, J. J. Neurosci. Res. (2004) [Pubmed]
  5. Neuroanatomical distribution of CXCR4 in adult rat brain and its localization in cholinergic and dopaminergic neurons. Banisadr, G., Fontanges, P., Haour, F., Kitabgi, P., Rostène, W., Mélik Parsadaniantz, S. Eur. J. Neurosci. (2002) [Pubmed]
  6. The chemokine SDF-1/CXCL12 modulates the firing pattern of vasopressin neurons and counteracts induced vasopressin release through CXCR4. Callewaere, C., Banisadr, G., Desarménien, M.G., Mechighel, P., Kitabgi, P., Rostène, W.H., Mélik Parsadaniantz, S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Expression of stromal cell-derived factor-1 and of its receptor CXCR4 in liver regeneration from oval cells in rat. Mavier, P., Martin, N., Couchie, D., Préaux, A.M., Laperche, Y., Zafrani, E.S. Am. J. Pathol. (2004) [Pubmed]
  8. The chemokine SDF-1 differentially regulates axonal elongation and branching in hippocampal neurons. Pujol, F., Kitabgi, P., Boudin, H. J. Cell. Sci. (2005) [Pubmed]
  9. Chemokine stromal cell-derived factor 1alpha induces proliferation and growth hormone release in GH4C1 rat pituitary adenoma cell line through multiple intracellular signals. Florio, T., Casagrande, S., Diana, F., Bajetto, A., Porcile, C., Zona, G., Thellung, S., Arena, S., Pattarozzi, A., Corsaro, A., Spaziante, R., Robello, M., Schettini, G. Mol. Pharmacol. (2006) [Pubmed]
  10. Immediate and neurotoxic effects of HIV protein gp120 act through CXCR4 receptor. Pandey, V., Bolsover, S.R. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  11. Cyclic AMP and tumor necrosis factor-alpha regulate CXCR4 gene expression in Schwann cells. Küry, P., Köller, H., Hamacher, M., Cornely, C., Hasse, B., Müller, H.W. Mol. Cell. Neurosci. (2003) [Pubmed]
  12. Identification of gp120 binding sites on CXCR4 by using CD4-independent human immunodeficiency virus type 2 Env proteins. Lin, G., Baribaud, F., Romano, J., Doms, R.W., Hoxie, J.A. J. Virol. (2003) [Pubmed]
  13. Stromal cell-derived factor 1 is secreted by meningeal cells and acts as chemotactic factor on neuronal stem cells of the cerebellar external granular layer. Reiss, K., Mentlein, R., Sievers, J., Hartmann, D. Neuroscience (2002) [Pubmed]
  14. Rat brain pericyte cell lines expressing beta2-adrenergic receptor, angiotensin II receptor type 1A, klotho, and CXCR4 mRNAs despite having endothelial cell markers. Asashima, T., Iizasa, H., Terasaki, T., Nakashima, E. J. Cell. Physiol. (2003) [Pubmed]
  15. Functional SDF1 alpha/CXCR4 signaling in the developing spinal cord. Luo, Y., Cai, J., Xue, H., Miura, T., Rao, M.S. J. Neurochem. (2005) [Pubmed]
  16. CXCL12 activation of CXCR4 regulates mucosal host defense through stimulation of epithelial cell migration and promotion of intestinal barrier integrity. Smith, J.M., Johanesen, P.A., Wendt, M.K., Binion, D.G., Dwinell, M.B. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  17. Peripheral nerve-derived HIV-1 is predominantly CCR5-dependent and causes neuronal degeneration and neuroinflammation. Jones, G., Zhu, Y., Silva, C., Tsutsui, S., Pardo, C.A., Keppler, O.T., McArthur, J.C., Power, C. Virology (2005) [Pubmed]
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