Journal article
NAC1 Regulates the Recruitment of the Proteasome Complex into Dendritic Spines
The Journal of neuroscience, Vol.27(33), pp.8903-8913
08/15/2007
DOI: 10.1523/JNEUROSCI.1571-07.2007
PMCID: PMC6672176
PMID: 17699672
Abstract
Coordinated proteolysis of synaptic proteins is required for synaptic plasticity, but a mechanism for recruiting the ubiquitin-proteasome system (UPS) into dendritic spines is not known. NAC1 is a cocaine-regulated transcriptional protein that was found to complex with proteins in the UPS, including cullins and Mov34. NAC1 and the proteasome were cotranslocated from the nucleus into dendritic spines in cortical neurons in response to proteasome inhibition or disinhibiting synaptic activity with bicuculline. Bicuculline also produced a progressive accumulation of the proteasome and NAC1 in the postsynaptic density. Recruitment of the proteasome into dendrites and postsynaptic density by bicuculline was prevented in neurons from mice harboring an NAC1 gene deletion or in neurons transfected with mutated NAC1 lacking the proteasome binding domain. These experiments show that NAC1 modulates the translocation of the UPS from the nucleus into dendritic spines, thereby suggesting a potential missing link in the recruitment of necessary proteolysis machinery for synaptic remodeling.
Details
- Title: Subtitle
- NAC1 Regulates the Recruitment of the Proteasome Complex into Dendritic Spines
- Creators
- Haowei Shen - Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425Laxminarayana Korutla - Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104Nicholas Champtiaux - Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425Shigenobu Toda - Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425Ryan LaLumiere - Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425Joseph Vallone - Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425Matthias Klugmann - Department of Neurobiology, Interdisciplinary Center for Neurosciences, University of Heidelberg, Heidelberg 69123, Germany, andJulie A Blendy - Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104Scott A Mackler - Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104Peter W Kalivas - Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.27(33), pp.8903-8913
- Publisher
- Society for Neuroscience
- DOI
- 10.1523/JNEUROSCI.1571-07.2007
- PMID
- 17699672
- PMCID
- PMC6672176
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 08/15/2007
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute
- Record Identifier
- 9984070391202771
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