HIV-1 gp120 Promotes Lysosomal Exocytosis in Human Schwann Cells

Frontiers in Cellular Neuroscience
Gaurav DattaXuesong Chen

Abstract

Human immunodeficiency virus type 1 (HIV-1) associated neuropathy is the most common neurological complication of HIV-1, with debilitating pain affecting the quality of life. HIV-1 gp120 plays an important role in the pathogenesis of HIV neuropathy via direct neurotoxic effects or indirect pro-inflammatory responses. Studies have shown that gp120-induced release of mediators from Schwann cells induce CCR5-dependent DRG neurotoxicity, however, CCR5 antagonists failed to improve pain in HIV- infected individuals. Thus, there is an urgent need for a better understanding of neuropathic pain pathogenesis and developing effective therapeutic strategies. Because lysosomal exocytosis in Schwann cells is an indispensable process for regulating myelination and demyelination, we determined the extent to which gp120 affected lysosomal exocytosis in human Schwann cells. We demonstrated that gp120 promoted the movement of lysosomes toward plasma membranes, induced lysosomal exocytosis, and increased the release of ATP into the extracellular media. Mechanistically, we demonstrated lysosome de-acidification, and activation of P2X4 and VNUT to underlie gp120-induced lysosome exocytosis. Functionally, we demonstrated that gp120-induced lysosome ...Continue Reading

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Citations

Jan 18, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nabab KhanXuesong Chen
Nov 11, 2019·Neurobiology of Disease·Zahra AfghahJonathan D Geiger
Dec 16, 2020·Membranes·Brunella TanciniLorena Urbanelli
Feb 27, 2021·Frontiers in Cell and Developmental Biology·Peter W HalcrowXuesong Chen
Jul 7, 2020·Cellular Signalling·Xuesong Chen, Jonathan D Geiger
Mar 23, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Koffi L LakpaJonathan D Geiger
Apr 10, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Peter W HalcrowJonathan D Geiger
May 8, 2021·Frontiers in Pharmacology·Huan-Jun LuZhi-Jun Zhang
Jul 12, 2020·Biochimica Et Biophysica Acta. Biomembranes·Nao HasuzawaMasatoshi Nomura

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Methods Mentioned

BETA
protein assay
Assay
Confocal microscopy
nuclear translocation
GTPases

Software Mentioned

Imaris XT
ZEISS ZEN
GraphPad Prism
Imaris
Imaris for Cell Biologists
Image J

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