Abstract
The HIV-1 envelope protein gp120IIIB is selective for the CXCR4 chemokine receptor and has been shown to induce apoptosis in neurons both in vivo and in vitro. We examined the ability of gp120IIIB to signal through the rat CXCR4 (rCXCR4) receptor and its dependence on the presence of the human CD4 (hCD4) protein in a number of cell systems. SDF-1α potently inhibited N-type Ca channels in cultured HEK293 cells expressing both the Ca channel subunits and rCXCR4 receptors. However, gp120IIIB was ineffective in producing either Ca channel inhibition or in blocking the effects of SDF-1α. However, when hCD4 was coexpressed with rCXCR4 and Ca channel subunits, gp120IIIB also produced Ca channel inhibition. Similarly, in PC12 cells transfected with the rCXCR4, SDF-1α produced mobilization of intracellular Ca, while gp120IIIB was only effective when hCD4 was coexpressed. SDF-1α induced endocytosis of Yellow Fluorescent Protein (YFP)-tagged rCXCR4 expressed in PC12 cells, as did gp120IIIB, an effect which was enhanced by hCD4 coexpression. When tagged rCXCR4 was expressed in F-11 cells or in rat DRG neurons, SDF-1α produced extensive receptor endocytosis. However, the ability of gp120IIIB to produce endocytosis was dependent on the coexpression of hCD4. Our results demonstrate that the degree of hCD4 dependence of the agonist effects of gp120IIIB at the rCXCR4 receptor is cell-type specific.
Original language | English (US) |
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Pages (from-to) | 1-12 |
Number of pages | 12 |
Journal | Journal of Neuroimmunology |
Volume | 140 |
Issue number | 1-2 |
DOIs | |
State | Published - Jul 2003 |
Funding
This work was supported by grants NIH NS43095, DA13141, MH40165, NS33826 and NS21442 to RJM. AB was supported in part by a fellowship award from Pharmaceutical Research and Manufacturers Association, and RKC was supported by grant HD-07009. The authors are grateful to Dr. B.R. Conklin (Gladstone Institute of Cardiovascular Disease, University of California) for the Giα-protein subunits chimeras. The authors appreciate the expert technical assistance of Christopher Mauer. The generous support from the NIH AIDS Research and Reference Reagent Program (gp120IIIB, soluble hCD4 and AMD3100) is greatly appreciated. This article is dedicated to the memory of Dr. Amos Bodner.
Keywords
- AIDS
- AMD3100
- Apoptosis
- Chemokine receptor
- Confocal microscopy
- Internalization
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
- Immunology and Allergy
- Immunology