Related Experiment Videos
Human CD38 and CD16 are functionally dependent and physically associated in natural killer cells
Silvia Deaglio1, Mercedes Zubiaur, Armando Gregorini
1Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, University of Torino Medical School, Via Santena 19, Turin, Italy.
Blood
|March 16, 2002
Summary
The CD38 molecule requires CD16 for signaling in natural killer (NK) cells. This interaction activates calcium fluxes, phosphorylation, and cytotoxic responses, revealing CD38
Area of Science:
- Immunology
- Cell Biology
- Molecular Signaling
Background:
- CD38 is a surface glycoprotein and ectoenzyme regulating calcium and cell interactions.
- CD38 ligation activates natural killer (NK) cell responses, but signaling mechanisms in CD16-negative NK lines were unclear.
Purpose of the Study:
- To identify the signaling molecule(s) that CD38 functionally cooperates with in NK cells.
- To elucidate the role of CD16 in CD38-mediated signaling pathways.
Main Methods:
- Genetic correction of CD16 expression in CD16-negative NK lines.
- Analysis of calcium fluxes, tyrosine phosphorylation (ZAP70, MAPK), cytokine secretion (IFN-γ), and cytotoxicity.
- Fluorescence resonance energy transfer (FRET) and cocapping experiments to assess molecular proximity.
Main Results:
- Functional CD16 expression is necessary and sufficient for CD38 to mediate NK cell activation.
- CD38 signaling involves calcium fluxes, ZAP70/MAPK phosphorylation, IFN-γ secretion, and cytotoxicity.
- Physical proximity between CD38 and CD16 was demonstrated, suggesting a direct interaction.
Conclusions:
- CD38 acts as a unique receptor that requires association with CD16 for signal transduction in NK cells.
- CD16 rescues CD38's receptor function through functional and physical interactions, highlighting lineage-specific signaling mechanisms.