MECHANISTIC STUDY ON THE ROLE OF ENDOCYTIC MACHINERY DURING NEURONAL PRUNING IN DROSOPHILA MELANOGASTER

Abstract

Selective removal of exuberant neuronal projections without cell death, referred to as pruning, is critical for the maturation of the nervous system. However, the mechanisms underlying neuronal pruning remain elusive. Here, utilizing Drosophila melanogaster as a model organism, I identified Rab5/ESCRT-dependent endocytic degradation pathways as novel players for dendrite-specific pruning in sensory neurons, ddaCs. Loss of Rab5/ESCRT results in dendrite pruning defects and ubiquitinated protein aggregates on aberrant endosomes. Importantly, cell adhesion molecule (CAM) Neuroglian (Nrg) accumulates on aberrant endosomes. Moreover, Nrg is relocalized on endosomes and downregulated prior to dendrite pruning in wild-type ddaC neurons. Overexpression of Nrg leads to dendrite pruning defects while loss of Nrg induces precocious pruning, indicating an inhibitory function in pruning. Lastly, attenuation of Nrg suppresses pruning defects of Rab5/ESCRT mutants. Collectively, downregulation of Nrg via endocytic degradation pathways to facilitate dendrite pruning in Drosophila sensory neurons reveals a novel mechanism in regulating neuronal pruning.