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

• Published in: PLoS biology 2018-08, Vol.16 (8), p.e2004506-e2004506
• Main Authors: Zong, Wenhui, Wang, Yan, Tang, Quan, Zhang, Heng, Yu, Fengwei
• Format: Article
• Language: English
• Subjects: Adaptin; Autophagy; Axons; Biology and Life Sciences; Cell adhesion; Cell adhesion molecules; Clathrin; Defects; Degradation; Dendrites; Drosophila; Insects; Kinases; Kinesin; Laboratories; Life sciences; Lysosomes; Nervous system; Neurodegeneration; Neurons; Proteins; Pruning; Research and Analysis Methods; Sensory neurons; Software
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.2004506

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.