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The HIV-1 coat protein gp120 regulates CXCR4-mediated signaling in neural progenitor cells
Phuong B Tran1, Dongjun Ren, Richard J Miller
1Department 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.
Abstract:
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.
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