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CD4 dependence of gp120IIIB-CXCR4 interaction is cell-type specific
Amos Bodner1, Peter T Toth, Seog Bae Oh
1Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 E. Chicago Avenue, Chicago, IL 60611, USA.
Journal of Neuroimmunology
|July 17, 2003
Summary
The HIV-1 envelope protein gp120IIIB requires human CD4 (hCD4) to effectively signal through rat CXCR4 (rCXCR4) receptors in some cells. This hCD4 dependence varies by cell type, impacting calcium channel activity and receptor endocytosis.
Area of Science:
- Neuroscience
- Virology
- Cell Biology
Background:
- The HIV-1 envelope protein gp120IIIB targets the CXCR4 chemokine receptor.
- gp120IIIB can induce neuronal apoptosis.
- CXCR4 plays a role in neuronal function.
Purpose of the Study:
- To investigate how gp120IIIB signals through rat CXCR4 (rCXCR4).
- To determine the role of human CD4 (hCD4) in gp120IIIB-mediated rCXCR4 signaling.
- To assess the cell-type specificity of hCD4 dependence.
Main Methods:
- Co-expression of rCXCR4, hCD4, and calcium channel subunits in HEK293 cells.
- Transfection of PC12 cells and F-11 cells with rCXCR4.
- Utilizing Yellow Fluorescent Protein (YFP)-tagged rCXCR4 for endocytosis studies.
- Assessing calcium channel inhibition and intracellular calcium mobilization.
Main Results:
- SDF-1alpha inhibited N-type Ca channels, but gp120IIIB did not, unless hCD4 was coexpressed.
- gp120IIIB induced intracellular calcium mobilization in PC12 cells only when hCD4 was present.
- gp120IIIB induced rCXCR4 endocytosis, an effect enhanced by hCD4, with cell-type specific variations.
Conclusions:
- The signaling of gp120IIIB through rCXCR4 is dependent on the coexpression of hCD4.
- This hCD4 dependence is specific to the cell type, influencing calcium channel activity and receptor endocytosis.
- Understanding this interaction is crucial for studying HIV-1 neuropathogenesis.