Phagocytosis and self-destruction break down dendrites of <i>Drosophila</i> sensory neurons at distinct steps of Wallerian degeneration
Hui Ji, Maria L. Sapar, Ankita Sarkar, Bei Wang, Chun Han
Abstract
Significance Mutations in the nicotinamide adenine dinucleotide (NAD + ) biosynthesis pathway are associated with progressive neurodegeneration; neuronal injury causes rapid breakdown of damaged axons and dendrites. NAD + reduction is thought to underlie both types of degeneration by inducing neuronal self-destruction. Here, we show that phagocytosis, instead of self-destruction, drives degeneration of Drosophila sensory dendrites in both injury and genetic NAD + disruptions. Mechanistically, phagocytosis is induced earlier than self-destruction by these manipulations, as a result of phosphatidylserine exposure on the dendrite surface. In addition, injured dendrites exhibit unique calcium dynamics and only partially require the axon-death factor Axed for self-destruction. Thus, our results suggest important contributions of phagocytosis to NAD + -related neurodegenerative diseases and highlight the difference between dendrite and axon degeneration.