CD4 dependence of gp120IIIB-CXCR4 interaction is cell-type specific

Amos Bodner; Peter T. Toth; Seog Bae Oh; Meiling Lu; Phuong B. Tran; Robert K. Chin; Dongjun Ren; Richard J. Miller

doi:10.1016/S0165-5728(03)00162-0

CD4 dependence of gp120IIIB-CXCR4 interaction is cell-type specific

Amos Bodner, Peter T. Toth, Seog Bae Oh, Meiling Lu, Phuong B. Tran, Robert K. Chin, Dongjun Ren, Richard J. Miller^*

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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)
Pages (from-to)	1-12
Number of pages	12
Journal	Journal of Neuroimmunology
Volume	140
Issue number	1-2
DOIs	https://doi.org/10.1016/S0165-5728(03)00162-0
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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0165-5728(03)00162-0

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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-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.",

keywords = "AIDS, AMD3100, Apoptosis, Chemokine receptor, Confocal microscopy, Internalization",

author = "Amos Bodner and Toth, {Peter T.} and Oh, {Seog Bae} and Meiling Lu and Tran, {Phuong B.} and Chin, {Robert K.} and Dongjun Ren and Miller, {Richard J.}",

note = "Funding Information: 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.",

year = "2003",

month = jul,

doi = "10.1016/S0165-5728(03)00162-0",

language = "English (US)",

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T1 - CD4 dependence of gp120IIIB-CXCR4 interaction is cell-type specific

AU - Bodner, Amos

AU - Toth, Peter T.

AU - Oh, Seog Bae

AU - Lu, Meiling

AU - Tran, Phuong B.

AU - Chin, Robert K.

AU - Ren, Dongjun

AU - Miller, Richard J.

N1 - Funding Information: 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.

PY - 2003/7

Y1 - 2003/7

N2 - 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.

AB - 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.

KW - AIDS

KW - AMD3100

KW - Apoptosis

KW - Chemokine receptor

KW - Confocal microscopy

KW - Internalization

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AN - SCOPUS:0038643825

SN - 0165-5728

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JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

IS - 1-2

ER -

CD4 dependence of gp120IIIB-CXCR4 interaction is cell-type specific

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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