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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Protein Complex alpha Subunits / genetics*
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Adaptor Protein Complex alpha Subunits / metabolism
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Animals
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Brain / cytology
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Brain / metabolism
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Cell Adhesion Molecules, Neuronal / genetics*
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Cell Adhesion Molecules, Neuronal / metabolism
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Dendrites / metabolism*
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Dendrites / ultrastructure
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Drosophila Proteins / genetics*
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Drosophila Proteins / metabolism
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Drosophila melanogaster / genetics*
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Drosophila melanogaster / growth & development
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Drosophila melanogaster / metabolism
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Endosomes / metabolism
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Endosomes / ultrastructure
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Gene Expression Regulation, Developmental
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Kinesins / genetics*
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Kinesins / metabolism
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Larva / genetics
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Larva / growth & development
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Larva / metabolism
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Lysosomes / metabolism
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Lysosomes / ultrastructure
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Metamorphosis, Biological / genetics
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Neural Cell Adhesion Molecule L1 / genetics*
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Neural Cell Adhesion Molecule L1 / metabolism
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Neuronal Plasticity / genetics*
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Protein Binding
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Proteolysis
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Sensory Receptor Cells / cytology
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Sensory Receptor Cells / metabolism
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Signal Transduction
Substances
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Adaptor Protein Complex alpha Subunits
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Cell Adhesion Molecules, Neuronal
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Drosophila Proteins
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Neural Cell Adhesion Molecule L1
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Nrg protein, Drosophila
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Unc-104 protein, Drosophila
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Kinesins
Grants and funding
Temasek Life Sciences Laboratory, Singapore (grant number TLL-2040). Received by FY. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.