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PMID: 21343367 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Neuronal remodeling and apoptosis require VCP-dependent degradation of the apoptosis inhibitor DIAP1.

Development (Cambridge, England) ·Vol. 138 ·No. 6 ·2011-03-00 ·Pages 1153-60

Rumpf S, Lee SB, Jan LY, Jan YN

Abstract

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 defects are associated with impaired caspase activation and high DIAP1 levels. In cultured cells, VCP binds to DIAP1 in a ubiquitin- and BIR domain-dependent manner and facilitates its degradation. Our results establish a new link between ubiquitin, dendrite pruning and the apoptosis machinery.

MeSH Terms
Adenosine Triphosphatases/antagonists & inhibitors,genetics,metabolism,physiology Animals Animals, Genetically Modified Apoptosis/genetics,physiology Apoptosis Regulatory Proteins/metabolism Caspases/metabolism Cell Cycle Proteins/antagonists & inhibitors,genetics,metabolism,physiology Cell Survival/genetics,physiology Cells, Cultured Dendrites/metabolism,physiology Drosophila/genetics,metabolism,physiology Drosophila Proteins/metabolism Inhibitor of Apoptosis Proteins/metabolism Models, Biological Neurons/metabolism,pathology,physiology Protein Processing, Post-Translational/genetics Stress, Physiological/genetics Valosin Containing Protein
Chemicals
Apoptosis Regulatory Proteins Cell Cycle Proteins DIAP1 protein, Drosophila Drosophila Proteins Inhibitor of Apoptosis Proteins Caspases Adenosine Triphosphatases Valosin Containing Protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Rumpf Sebastian
Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.
Lee Sung Bae
Jan Lily Yeh
Jan Yuh Nung
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Article Info
Journal
Development (Cambridge, England)
Abbr.
Development
ISSN
1477-9129
DOI
10.1242/dev.062703
Published
2011-03-00
Pages
1153-60
Language
English
Region
England
NLM ID
8701744
PMCID
PMC3042870
Subset
IM
Grants
NINDS NIH HHS · R 37NS040929 · United States
Howard Hughes Medical Institute · United States
External Links
PubMed source DOI: 10.1242/dev.062703 PMC Full Text View journal details
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