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Updated: May 23, 2026

Assessing the Cellular Immune Response of the Fruit Fly, Drosophila melanogaster, Using an In Vivo Phagocytosis Assay
Published on: April 10, 2019
Phosphoinositide binding by the Toll adaptor dMyD88 controls antibacterial responses in Drosophila
Lorri R Marek1, Jonathan C Kagan
1Division of Gasteroenterology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Abstract:
The cell biological principles that govern innate immune responses in Drosophila are unknown. Here, we report that Toll signaling in flies was dictated by the subcellular localization of the adaptor protein dMyD88. dMyD88 was located at the plasma membrane by a process dependent on a C-terminal phosphoinositide-binding domain. In vivo analysis revealed that lipid binding by dMyD88 was necessary for its antimicrobial and developmental functions as well as for the recruitment of the downstream cytosolic adaptor Tube to the cell surface. These data are reminiscent of the interactions between the mammalian Toll adaptors MyD88 and TIRAP with one major exception. In the mammalian system, MyD88 is the cytosolic adaptor that depends on the phosphoinositide-binding protein TIRAP for its recruitment to the cell surface. We therefore propose that dMyD88 is the functional homolog of TIRAP and that both proteins function as sorting adaptors to recruit downstream signaling adaptors to activated receptors.
Insights
Drosophila Toll signaling relies on the adaptor protein dMyD88
Area of Science:
- Cell Biology
- Immunology
- Genetics
Background:
- Innate immune responses in Drosophila are not well understood.
- Toll signaling is crucial for Drosophila immunity.
Purpose of the Study:
- To elucidate the cell biological principles governing Drosophila innate immunity.
- To investigate the role of the adaptor protein dMyD88 in Toll signaling.
Main Methods:
- Subcellular localization studies of dMyD88.
- In vivo analysis of dMyD88 function.
- Investigating phosphoinositide-binding domain activity.
Main Results:
- dMyD88 localization to the plasma membrane is essential for Toll signaling.
- A C-terminal phosphoinositide-binding domain mediates dMyD88 membrane localization.
- Lipid binding by dMyD88 is critical for antimicrobial and developmental functions.
- dMyD88 recruits the downstream adaptor Tube to the cell surface.
Conclusions:
- dMyD88 acts as a sorting adaptor in Drosophila Toll signaling.
- dMyD88 is functionally homologous to mammalian TIRAP.
- This study reveals key cell biological mechanisms of innate immunity in Drosophila.
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