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Extracellular ATP induces unconventional release of glyceraldehyde-3-phosphate dehydrogenase from microglial cells
- Source :
- Immunology Letters. (2):116-124
- Publisher :
- The Authors. Published by Elsevier B.V.
-
Abstract
- Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme that is predominantly localized in the cytoplasm. However, recent studies have suggested that GAPDH is released by various cells and that extracellular GAPDH is involved in the regulation of neuritogenesis in neuronal cells. It has also been reported that GAPDH is expressed on the surfaces of macrophages and functions as a transferrin receptor. However, since GAPDH is a leaderless protein the mechanisms by which it reaches the extracellular environment remain unclear. Here, we examined the role of P2X7 receptor (P2X7R), an ATP-gated cation channel, in the unconventional release of GAPDH from microglial cells, the resident macrophages in the brain. The activation of P2X7R by ATP triggered GAPDH release from lipopolysaccharide (LPS)-primed microglial cells. ATP-induced microvesicle formation, exosome release, and K+ efflux followed by caspase-1 activation are likely involved in the GAPDH release, but ATP-induced dilatation of membrane pores and lysosome exocytosis are not. It was also demonstrated that exogenous GAPDH facilitated LPS-induced phosphorylation of p38 MAP kinase in microglial cells. These findings suggest that P2X7R plays an important role in the unconventional release of GAPDH from microglial cells, and the GAPDH released into the extracellular space might be involved in the regulation of the neuroinflammatory response in the brain.
- Subjects :
- Lipopolysaccharides
Primary Cell Culture
Immunology
Enzyme-Linked Immunosorbent Assay
Transferrin receptor
p38 Mitogen-Activated Protein Kinases
Exocytosis
Adenosine Triphosphate
stomatognathic system
Lysosome
Extracellular
medicine
Humans
Immunology and Allergy
Phosphorylation
Unconventional release
Cells, Cultured
Glyceraldehyde 3-phosphate dehydrogenase
Microglia
biology
Microvesicle
Caspase 1
Glyceraldehyde-3-Phosphate Dehydrogenases
Immunohistochemistry
Cell biology
Enzyme Activation
medicine.anatomical_structure
Biochemistry
Cell culture
P2X7 receptor
Potassium
biology.protein
Glyceraldehyde-3-phosphate dehydrogenase
Receptors, Purinergic P2X7
Extracellular Space
Lysosomes
Microglial cells
Subjects
Details
- Language :
- English
- ISSN :
- 01652478
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Immunology Letters
- Accession number :
- edsair.doi.dedup.....9bd6a7792e1f9352780857540645038c
- Full Text :
- https://doi.org/10.1016/j.imlet.2015.08.002