Drosophila Valosin-Containing Protein is required for dendrite pruning through a regulatory role in mRNA metabolism
Drosophila Valosin-Containing Protein is required for dendrite pruning through a regulatory role in mRNA metabolism
Significance The ubiquitin–proteasome system (UPS) is required for Drosophila class IV dendritic arborization neuron dendrite pruning. We found that mutants in the ubiquitylation machinery, the ubiquitin-dependent chaperone Valosin-Containing Protein ( VCP ), and the 19S regulatory particle of the proteasome—but not the 20S core particle—showed defects in pruning gene expression and mislocalization or overexpression of specific mRNA-binding proteins. In the case of VCP inhibition, we were able to detect a specific change in the splicing pattern of a pruning gene that likely contributes to pruning defects. A link between VCP and mRNA-binding proteins had been observed in the context of human neurodegenerative disease. This study implicates a specific function of VCP and ubiquitin in mRNA metabolism.
- University of Georgia Georgia
- Howard Hughes Medical Institute United States
- University of Georgia Press United States
- University of California, San Francisco United States
Ecdysone, Proteasome Endopeptidase Complex, Messenger, Neurodegenerative, Valosin Containing Protein, Genetics, Animals, Drosophila Proteins, RNA, Messenger, Adenosine Triphosphatases, Neurons, Biomedical and Clinical Sciences, Ubiquitin, Neurosciences, RNA-Binding Proteins, Dendrites, Biological Sciences, DNA-Binding Proteins, Drosophila melanogaster, Phenotype, Gene Expression Regulation, Neurological, Mutation, RNA, Biochemistry and Cell Biology, Protein Binding, Signal Transduction
Ecdysone, Proteasome Endopeptidase Complex, Messenger, Neurodegenerative, Valosin Containing Protein, Genetics, Animals, Drosophila Proteins, RNA, Messenger, Adenosine Triphosphatases, Neurons, Biomedical and Clinical Sciences, Ubiquitin, Neurosciences, RNA-Binding Proteins, Dendrites, Biological Sciences, DNA-Binding Proteins, Drosophila melanogaster, Phenotype, Gene Expression Regulation, Neurological, Mutation, RNA, Biochemistry and Cell Biology, Protein Binding, Signal Transduction
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