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Barbadin selectivel...
Barbadin selectively modulates FPR2-mediated neutrophil functions independent of receptor endocytosis
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- Sundqvist, Martina (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Holdfeldt, André (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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Wright, S. C. (author)
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Moller, T. C. (author)
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- Siaw, Esther (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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Jennbacken, K. (author)
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Franzyk, H. (author)
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Bouvier, M. (author)
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- Dahlgren, Claes, 1949 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Forsman, Huamei (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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(creator_code:org_t)
- Elsevier BV, 2020
- 2020
- English.
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In: Biochimica Et Biophysica Acta-Molecular Cell Research. - : Elsevier BV. - 0167-4889. ; 1867:12
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Abstract
Subject headings
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- FPR2, a member of the family of G protein-coupled receptors (GPCRs), mediates neutrophil migration, a response that has been linked to beta-arrestin recruitment. beta-Arrestin regulates GPCR endocytosis and can also elicit non-canonical receptor signaling. To determine the poorly understood role of beta-arrestin in FPR2 endocytosis and in NADPH-oxidase activation in neutrophils, Barbadin was used as a research tool in this study. Barbadin has been shown to bind the clathrin adaptor protein (AP2) and thereby prevent beta-arrestin/AP2 interaction and beta-arrestin-mediated GPCR endocytosis. In agreement with this, AP2/beta-arrestin interaction induced by an FPR2-specific agonist was inhibited by Barbadin. Unexpectedly, however, Barbadin did not inhibit FPR2 endocytosis, indicating that a mechanism independent of beta-arrestin/AP2 interaction may sustain FPR2 endocytosis. This was confirmed by the fact, that FPR2 also underwent agonist-promoted endocytosis in beta-arrestin deficient cells, albeit at a diminished level as compared to wild type cells. Dissection of the Barbadin effects on FPR2-mediated neutrophil functions including NADPH-oxidase activation mediated release of reactive oxygen species (ROS) and chemotaxis revealed that Barbadin had no effect on chemotactic migration whereas the release of ROS was potentiated/primed. The effect of Barbadin on ROS production was reversible, independent of beta-arrestin recruitment, and similar to that induced by latrunculin A. Taken together, our data demonstrate that endocytic uptake of FPR2 occurs independently of beta-arrestin, while Barbadin selectively augments FPR2-mediated ROS production independently of receptor endocytosis. Given that Barbadin binds to AP2 and prevents the AP2/beta-arrestin interaction, our results indicate a role for AP2 in FPR2-mediated ROS release from neutrophils.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- G protein-coupled receptors
- FPR2
- AP2
- Actin cytoskeleton
- Barbadin
- beta-Arrestin
- Desensitization
- Resensitization
- Endocytosis
- Neutrophils
- Reactive oxygen species
- beta-arrestin recruitment
- formyl peptide receptors
- nadph-oxidase
- fpr2
- granulocytes
- cytoskeleton
- activation
- agonist
- blood
- Biochemistry & Molecular Biology
- Cell Biology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Sundqvist, Marti ...
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Holdfeldt, André
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Wright, S. C.
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Moller, T. C.
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Siaw, Esther
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Jennbacken, K.
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show more...
-
Franzyk, H.
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Bouvier, M.
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Dahlgren, Claes, ...
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Forsman, Huamei
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
- Articles in the publication
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Biochimica Et Bi ...
- By the university
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University of Gothenburg