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bioRxiv · 10.1101/2020.06.26.173245

Phagocytosis drives NAD+ reduction-induced dendrite degeneration in Drosophila

Sapar, M. L.·Sarkar, A.·Ji, H.·Wang, B.·Han, C.
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Abstract

After injury, severed dendrites and axons expose the "eat-me" signal phosphatidylserine (PS) on their surface and degenerate by disassembly. While axon degeneration is controlled by a conserved "axon-death" pathway that is thought to activate self-destruction, how PS exposure is regulated by this pathway and whether PS-induced phagocytosis contributes to neurite breakdown in vivo remain unknown. Here we show that in Drosophila sensory dendrites, PS exposure and self-destruction are triggered by two distinct levels of NAD+ reduction downstream of Sarm activation. Surprisingly, phagocytosis is the main driver of dendrite degeneration induced by both genetic NAD+ disruptions and injury. Furthermore, the axon-death factor Axed is only partially required for self-destruction of injured dendrites, acting in parallel with PS-induced phagocytosis. Lastly, injured dendrites exhibit a unique rhythmic calcium flashing that correlates with self-destruction. Therefore, a special genetic program coordinates PS exposure and self-destruction in injury-induced dendrite degeneration in vivo.

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Sapar, M. L., Sarkar, A., Ji, H., Wang, B., Han, C.. 2020-06-26. Phagocytosis drives NAD+ reduction-induced dendrite degeneration in Drosophila. https://doi.org/10.1101/2020.06.26.173245

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