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Nitric oxide regulates phagocytosis through S-nitrosylation of Rab5
Makoto Hagiwara1, Hiroyuki Tada2, Kenji Matsushita3
1Department of Health and Nutrition, Faculty of Human Life Studies, University of Niigata Prefecture, Niigata-city, Niigata, Japan.
The Journal of Biological Chemistry
|September 10, 2025
Summary
Nitric oxide (NO) activates the small GTP-binding protein Rab5 through S-nitrosylation, enhancing phagocytosis. This discovery reveals NO as a key regulator of immune cell bacterial clearance.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Phagocytosis is a critical immune process mediated by cells like macrophages.
- The small GTP-binding protein Rab5 is essential for phagocytosis, but its activation mechanism remains unclear.
Purpose of the Study:
- To investigate the role of nitric oxide (NO) in regulating Rab5 activation and phagocytosis.
- To elucidate the mechanism by which NO influences Rab5 activity.
Main Methods:
- Utilized cultured cells and mouse models to study NO's effect on Rab5.
- Investigated S-nitrosylation of Rab5, focusing on specific cysteine residues.
- Assessed phagocytic activity and bacterial clearance in peritoneal macrophages.
Main Results:
- Nitric oxide (NO) was identified as a novel regulator that promotes phagocytosis by activating Rab5.
- NO specifically S-nitrosylates active Rab5 at two C-terminal cysteine residues, enhancing its function.
- In vivo studies confirmed NO's role in activating Rab5 and facilitating bacterial clearance by macrophages.
Conclusions:
- Nitric oxide (NO) promotes phagocytosis via S-nitrosylation and activation of Rab5.
- This mechanism highlights NO as a crucial regulator of immune cell function and bacterial clearance.
Keywords:
GEF-like actionRab5S-nitrosylationcysteine residuesiNOSimmunityinfectionlipopolysaccharidemembrane traffickingnitric oxidephagocytic cellsphagocytosisprenylation-independentredox reactionsmall GTPaseMore Related Videos
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