Phagocytosis and self-destruction break down dendrites of Drosophila sensory neurons at distinct steps of Wallerian degeneration
Proceedings of the National Academy of Sciences, 2022•National Acad Sciences
After injury, severed dendrites and axons expose the “eat-me” signal phosphatidylserine
(PS) on their surface while they break down. The degeneration of injured axons is controlled
by a conserved Wallerian degeneration (WD) pathway, which is thought to activate neurite
self-destruction through Sarm-mediated nicotinamide adenine dinucleotide (NAD+)
depletion. While neurite PS exposure is known to be affected by genetic manipulations of
NAD+, how the WD pathway coordinates both neurite PS exposure and self-destruction and …
(PS) on their surface while they break down. The degeneration of injured axons is controlled
by a conserved Wallerian degeneration (WD) pathway, which is thought to activate neurite
self-destruction through Sarm-mediated nicotinamide adenine dinucleotide (NAD+)
depletion. While neurite PS exposure is known to be affected by genetic manipulations of
NAD+, how the WD pathway coordinates both neurite PS exposure and self-destruction and …
After injury, severed dendrites and axons expose the “eat-me” signal phosphatidylserine (PS) on their surface while they break down. The degeneration of injured axons is controlled by a conserved Wallerian degeneration (WD) pathway, which is thought to activate neurite self-destruction through Sarm-mediated nicotinamide adenine dinucleotide (NAD+) depletion. While neurite PS exposure is known to be affected by genetic manipulations of NAD+, how the WD pathway coordinates both neurite PS exposure and self-destruction 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 two sequential steps of WD resulting from Sarm activation. Surprisingly, phagocytosis is the main driver of dendrite degeneration induced by both genetic NAD+ disruptions and injury. However, unlike neuronal Nmnat loss, which triggers PS exposure only and results in phagocytosis-dependent dendrite degeneration, injury activates both PS exposure and self-destruction as two redundant means of dendrite degeneration. 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 WD. Therefore, both NAD+-related general mechanisms and dendrite-specific programs govern PS exposure and self-destruction in injury-induced dendrite degeneration in vivo.
National Acad Sciences