The

Area of Science:

• Neuroscience
• Cell Biology
• Immunology

Background:

• Phagocytosis of degenerating neurons is crucial for tissue homeostasis.
• The neuronal
• eat-me
• signal phosphatidylserine (PS) and the engulfment receptor Draper (Drpr) are known mediators of this process in Drosophila.
• The precise mechanism by which PS is recognized by Drpr-expressing phagocytes in vivo is not fully understood.

Purpose of the Study:

• To elucidate the mechanism of phosphatidylserine (PS) recognition by Draper (Drpr)-expressing phagocytes during neuronal degeneration in Drosophila.
• To identify novel factors involved in mediating the interaction between PS and Drpr.

Main Methods:

• Utilized multiple Drosophila models of dendrite degeneration.
• Investigated the role of the chemokine-like protein Orion in PS recognition.
• Performed mutagenesis analyses to identify functional domains of Orion.

Main Results:

• Demonstrated that the Drosophila chemokine-like protein Orion binds to PS and detects its exposure on neurons.
• Showed that Orion is supplied cell-non-autonomously to coat PS-exposing dendrites, facilitating the interaction between PS and Drpr.
• Found that Orion accumulation on neurons potentiates phagocytosis, while its accumulation on phagocytes suppresses it.
• Identified conserved sequence motifs in Orion important for its function, suggesting links to human immunomodulatory proteins.

Conclusions:

• Orion acts as a crucial missing link in PS-mediated phagocytosis of degenerating neurons in Drosophila.
• Orion's dosage is a key determinant of phagocyte sensitivity to neuronal PS.
• The findings imply conserved mechanisms for neuronal phagocytosis across species.