Open AccessPhagocytosis and self-destruction break down dendrites of Drosophila sensory neurons at distinct steps of Wallerian degeneration
Author(s) -
Hui Ji,
Maria L. Sapar,
Ankita Sarkar,
Bei Wang,
Chun Han
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2111818119
Subject(s) - wallerian degeneration , dendrite (mathematics) , neurite , phagocytosis , nad+ kinase , microbiology and biotechnology , degeneration (medical) , axon , nicotinamide adenine dinucleotide , biology , axotomy , neurodegeneration , neuroscience , programmed cell death , chemistry , biochemistry , apoptosis , pathology , medicine , in vitro , regeneration (biology) , enzyme , geometry , mathematics , disease
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 ofDrosophila 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.