biostudies-literatureRumpf SHoward Hughes Medical InstituteNINDS NIH HHS1153-60https://www.ebi.ac.uk/biostudies/studies/S-EPMC3042870biostudies-literatureUnknown138(6)The regulated degeneration of axons or dendrites (pruning) and neuronal apoptosis are widely used during development to determine the specificity of neuronal connections. Pruning and apoptosis often share similar mechanisms; for example, developmental dendrite pruning of Drosophila class IV dendritic arborization (da) neurons is induced by local caspase activation triggered by ubiquitin-mediated degradation of the caspase inhibitor DIAP1. Here, we examined the function of Valosin-containing protein (VCP), a ubiquitin-selective AAA chaperone involved in endoplasmic reticulum-associated degradation, autophagy and neurodegenerative disease, in Drosophila da neurons. Strong VCP inhibition is cell lethal, but milder inhibition interferes with dendrite pruning and developmental apoptosis. These Development (Cambridge, England)Neuronal remodeling and apoptosis require VCP-dependent degradation of the apoptosis inhibitor DIAP1.PMC3042870R 37NS040929Jan LYRumpf SLee SBJan YNfalseNeuronal remodeling and apoptosis require VCP-dependent degradation of the apoptosis inhibitor DIAP1.The regulated degeneration of axons or dendrites (pruning) and neuronal apoptosis are widely used during development to determine the specificity of neuronal connections. Pruning and apoptosis often share similar mechanisms; for example, developmental dendrite pruning of Drosophila class IV dendritic arborization (da) neurons is induced by local caspase activation triggered by ubiquitin-mediated degradation of the caspase inhibitor DIAP1. Here, we examined the function of Valosin-containing protein (VCP), a ubiquitin-selective AAA chaperone involved in endoplasmic reticulum-associated degradation, autophagy and neurodegenerative disease, in Drosophila da neurons. Strong VCP inhibition is cell lethal, but milder inhibition interferes with dendrite pruning and developmental apoptosis. These 2011-01-01T00:00:00Z2011 Mar2025-04-19T21:12:56.626Z2019-03-27T00:39:08ZS-EPMC30428702134336710.1242/dev.062703