Prd1 associates with the clathrin adaptor α-Adaptin and the kinesin-3 Imac/Unc-104 to govern dendrite pruning in Drosophila.

Wenhui Zong,Fengwei Yu,Quan Tang,Heng Zhang,Yan Wang,Marc Freeman

doi:10.1371/journal.pbio.2004506

Abstract

Refinement of the nervous system depends on selective removal of excessive axons/dendrites, a process known as pruning. Drosophila ddaC sensory neurons prune their larval dendrites via endo-lysosomal degradation of the L1-type cell adhesion molecule (L1-CAM), Neuroglian (Nrg). Here, we have identified a novel gene, pruning defect 1 (prd1), which governs dendrite pruning of ddaC neurons. We show that Prd1 colocalizes with the clathrin adaptor protein α-Adaptin (α-Ada) and the kinesin-3 immaculate connections (Imac)/Uncoordinated-104 (Unc-104) in dendrites. Moreover, Prd1 physically associates with α-Ada and Imac, which are both critical for dendrite pruning. Prd1, α-Ada, and Imac promote dendrite pruning via the regulation of endo-lysosomal degradation of Nrg. Importantly, genetic interactions among prd1, α-adaptin, and imac indicate that they act in the same pathway to promote dendrite pruning. Our findings indicate that Prd1, α-Ada, and Imac act together to regulate discrete distribution of α-Ada/clathrin puncta, facilitate endo-lysosomal degradation, and thereby promote dendrite pruning in sensory neurons.

Highlights

Neuronal remodeling is a pivotal step in the formation of mature nervous systems during animal development
In Drosophila, a class of sensory neurons lose all their larval dendrites during metamorphosis, when they transition from larvae to adults
We identified a previously uncharacterized gene, pruning defect 1, which plays an important role in dendrite pruning

Summary

Introduction

Neuronal remodeling is a pivotal step in the formation of mature nervous systems during animal development. In the central and peripheral nervous systems of mammals, many neurons often prune their unwanted or inappropriate neurites in order to establish proper and functional neuronal connections [4,5,6]. In insects, such as Drosophila, the nervous system is drastically remodeled during metamorphosis [7,8,9]. In the central nervous system, mushroom body (MB) γ neurons prune their larval axonal/dendritic branches and extend their adult-specific processes to be integrated into the adult brains prior to eclosion [10]. Understanding the mechanisms of developmental pruning would provide insight into neurodegeneration in pathological conditions

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Conclusion