title: CD4 dependence of gp120IIIB-CXCR4 interaction is cell-type specific.
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-1alpha 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-1alpha. 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-1alpha produced mobilization of intracellular Ca, while gp120IIIB was only effective when hCD4 was coexpressed. SDF-1alpha 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-1alpha 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.
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 E. Chicago Avenue, Chicago, IL 60611, USA.
authors.forename: Amos
authors.initials: A
authors.lastname: Bodner
authors.forename: Peter T
authors.initials: PT
authors.lastname: Toth
authors.forename: Seog Bae
authors.initials: SB
authors.lastname: Oh
authors.forename: Meiling
authors.initials: M
authors.lastname: Lu
authors.forename: Phuong B
authors.initials: PB
authors.lastname: Tran
authors.forename: Robert K
authors.initials: RK
authors.lastname: Chin
authors.forename: Dongjun
authors.initials: D
authors.lastname: Ren
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Miller
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000276:immunology; D015704:CD4 Antigens / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D004705:Endocytosis / Q000235:genetics / Q000276:immunology; D005727:Ganglia, Spinal / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D019707:Receptors, Chemokine; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D015704:CD4 Antigens; C486264:Cxcr4 protein, rat; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine