The HIV-1 coat protein gp120 regulates CXCR4-mediated signaling in neural progenitor cells.
We demonstrate that hCD4-primed gp120IIIB interacts with CXCR4 receptors expressed by postnatal mouse neural progenitor cells and elicits robust Ca(2+) signals. The chemokine SDF-1 acted as a chemoattractant and a mitogenic stimulus for these neural progenitor cells. Although hCD4/gp120 was not able to produce chemoattraction or increase proliferation, it completely blocked the ability of SDF-1 to produce these effects. Thus, gp120 can act both as an agonist and de facto antagonist of CXCR4-mediated signaling in neural progenitor cells. It is possible that the ability of hCD4/gp120 to block SDF-1 signaling in neural progenitors may contribute to the neuropathological effects of HIV-1.
Tran
Phuong B
PB
Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, MPBC, m/c S215 W8-296, 303 E Chicago Ave., Chicago, IL 60611, USA.
Ren
Dongjun
D
Miller
Richard J
RJ
D000818:Animals; D015704:CD4 Antigens / Q000502:physiology; D020013:Calcium Signaling / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism / Q000502:physiology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D013234:Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology
D015704:CD4 Antigens; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4