Endocytic Pathways Downregulate the L1-type Cell Adhesion Molecule Neuroglian to Promote Dendrite Pruning in Drosophila

•Rab5/ESCRT-dependent endocytic pathways promote dendrite pruning of ddaC neurons•Nrg plays a critical inhibitory role in dendrite pruning in ddaC neurons•Rab5 and ESCRT downregulate Nrg in ddaC neurons prior to dendrite pruning•Rab5 and ESCRT restrain Nrg function to promote ddaC dendrite pruning

SummaryPruning of unnecessary axons and/or dendrites is crucial for maturation of the nervous system. However, little is known about cell adhesion molecules (CAMs) that control neuronal pruning. In Drosophila, dendritic arborization neurons, ddaCs, selectively prune their larval dendrites. Here, we report that Rab5/ESCRT-mediated endocytic pathways are critical for dendrite pruning. Loss of Rab5 or ESCRT function leads to robust accumulation of the L1-type CAM Neuroglian (Nrg) on enlarged endosomes in ddaC neurons. Nrg is localized on endosomes in wild-type ddaC neurons and downregulated prior to dendrite pruning. Overexpression of Nrg alone is sufficient to inhibit dendrite pruning, whereas removal of Nrg causes precocious dendrite pruning. Epistasis experiments indicate that Rab5 and ESCRT restrain the inhibitory role of Nrg during dendrite pruning. Thus, this study demonstrates the cell-surface molecule that controls dendrite pruning and defines an important mechanism whereby sensory neurons, via endolysosomal pathway, downregulate the cell-surface molecule to trigger dendrite pruning.