NAC1 Regulates the Recruitment of the Proteasome Complex into Dendritic Spines

Shen, Haowei; Korutla, Laxminarayana; Champtiaux, Nicholas; Toda, Shigenobu; LaLumiere, Ryan T.; Vallone, Joseph; Klugmann, Matthias; Blendy, Julie A.; Mackler, Scott A.; Kalivas, Peter W.

doi:10.1523/jneurosci.1571-07.2007

Cited by 55 publications

(60 citation statements)

References 53 publications

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“…Shen et al have recently demonstrated that proteasome inhibition or bicuculline disinhibition in cultured hippocampal neurons caused translocation of the proteasome from nucleus to cytoplasm [114]. We have discovered a similar shift of UPS components from nucleus to cytoplasm upon transgenic proteasome inhibition in Drosophila, where ubiquitinated proteins no longer accumulated in the nucleus after acute proteasome inhibition (Fig.…”

Section: Ups Trafficking In Synapse Regulationsupporting

confidence: 59%

“…Shen et al show that a 19S ATPase regulatory proteasome subunit, Mov34, complexes with a subunit of the SCF E3 ligase complex, Cul3, and an immediate early gene, NAC1, that is upregulated after psychostimulant-induced behavioral plasticity. Heightened synaptic activity promotes rapid and persistent NAC1-dependent translocation of the proteasome and Cul3 to the region of postsynaptic dendritic spines [114]. The activity-dependent trafficking of proteasomes and associated UPS machinery provides an exciting mechanism for tuning local protein degradation by coupling synaptic activity levels with proteasome availability.…”

Section: Ups Trafficking In Synapse Regulationmentioning

confidence: 99%

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Roles of ubiquitination at the synapse

Haas

Broadie

2008

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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The ubiquitin proteasome system (UPS) was first described as a mechanism for protein degradation more than three decades ago, but the critical roles of the UPS in regulating neuronal synapses have only recently begun to be revealed. Targeted ubiquitination of synaptic proteins affects multiple facets of the synapse throughout its life cycle; from synaptogenesis and synapse elimination to activity-dependent synaptic plasticity and remodeling. The recent identification of specific UPS molecular pathways that act locally at the synapse illustrates the exquisite specificity of ubiquitination in regulating synaptic protein trafficking and degradation events. Synaptic activity has also been shown to determine the subcellular distribution and composition of the proteasome, providing additional mechanisms for locally regulating synaptic protein degradation. Together these advances reveal that tight control of protein turnover plays a conserved, central role in establishing and modulating synapses in neural circuits.

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Section: Ups Trafficking In Synapse Regulationsupporting

confidence: 59%

Section: Ups Trafficking In Synapse Regulationmentioning

confidence: 99%

Roles of ubiquitination at the synapse

Haas

Broadie

2008

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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“…This redistribution was found to be dependent upon NMDA receptor activation (63). A subsequent report showed that NAC1, a cocaine-regulated transcriptional protein that interacts with the proteasome, regulates the trafficking of the proteasome in an activity-dependent manner (64). These data suggest that synaptic activity can promote the recruitment and sequestration of proteasomes to locally remodel the protein composition of synapses.…”

Section: Discussionmentioning

confidence: 87%

“…Because CaMKII-dependent phosphorylation of Rpt6 did not directly regulate proteasome activity in vitro, we hypothesize that other regulatory factors, not present in our reconstituted and highly purified in vitro assay, may be required. Associated proteins have previously been found to regulate various aspects of proteasome function (23,64,74). Interestingly, both proteasome and CaMKII translocate from dendritic shaft to dendritic spine compartments in response to neuronal activity in a similar timeframe (63,75,76).…”

Section: Discussionmentioning

confidence: 95%

Regulation of the Proteasome by Neuronal Activity and Calcium/Calmodulin-dependent Protein Kinase II

Djakovic

Schwarz

Baryłko

et al. 2009

Journal of Biological Chemistry

212

213

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Protein degradation via the ubiquitin proteasome system has been shown to regulate changes in synaptic strength that underlie multiple forms of synaptic plasticity. It is plausible, therefore, that the ubiquitin proteasome system is itself regulated by synaptic activity. By utilizing live-cell imaging strategies we report the rapid and dynamic regulation of the proteasome in hippocampal neurons by synaptic activity. We find that the blockade of action potentials (APs) with tetrodotoxin inhibited the activity of the proteasome, whereas the up-regulation of APs with bicuculline dramatically increased the activity of the proteasome. In addition, the regulation of the proteasome is dependent upon external calcium entry in part through N-methyl-D-aspartate receptors and L-type voltage-gated calcium channels and requires the activity of calcium/calmodulindependent protein kinase II (CaMKII). Using in vitro and in vivo assays we find that CaMKII stimulates proteasome activity and directly phosphorylates Rpt6, a subunit of the 19 S (PA700) subcomplex of the 26 S proteasome. Our data provide a novel mechanism whereby CaMKII may regulate the proteasome in neurons to facilitate remodeling of synaptic connections through protein degradation.

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“…It will also be important to uncover molecular mechanisms linking cocaine to UPS regulation (eg, Shen et al, 2007). However, our study-the first to examine the role of the UPS in retrieval of cocaine memories following cocaine selfadministration, as well as the first to examine the UPS following retrieval in any operant learning paradigm or after a delay between training and testing-provides an important framework for future studies by revealing that the involvement of the UPS in memory retrieval depends greatly upon paradigm, brain region, and the age of the memory.…”

Section: Discussionmentioning

confidence: 99%

Response of the Ubiquitin-Proteasome System to Memory Retrieval After Extended-Access Cocaine or Saline Self-Administration

Werner

Milovanovic

Christian

et al. 2015

Neuropsychopharmacol

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The ubiquitin-proteasome system (UPS) has been implicated in the retrieval-induced destabilization of cocaine-and fear-related memories in Pavlovian paradigms. However, nothing is known about its role in memory retrieval after self-administration of cocaine, an operant paradigm, or how the length of withdrawal from cocaine may influence retrieval mechanisms. Here, we examined UPS activity after an extended-access cocaine self-administration regimen that leads to withdrawal-dependent incubation of cue-induced cocaine craving. Controls self-administered saline. In initial experiments, memory retrieval was elicited via a cue-induced seeking/retrieval test on withdrawal day (WD) 50-60, when craving has incubated. We found that retrieval of cocaine-and saline-associated memories produced similar increases in polyubiquitinated proteins in the nucleus accumbens (NAc), compared with rats that did not undergo a seeking/retrieval test. Measures of proteasome catalytic activity confirmed similar activation of the UPS after retrieval of saline and cocaine memories. However, in a subsequent experiment in which testing was conducted on WD1, proteasome activity in the NAc was greater after retrieval of cocaine memory than saline memory. Analysis of other brain regions confirmed that effects of cocaine memory retrieval on proteasome activity, relative to saline memory retrieval, depend on withdrawal time. These results, combined with prior studies, suggest that the relationship between UPS activity and memory retrieval depends on training paradigm, brain region, and time elapsed between training and retrieval. The observation that mechanisms underlying cocaine memory retrieval change depending on the age of the memory has implications for development of memory destabilization therapies for cue-induced relapse in cocaine addicts.

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NAC1 Regulates the Recruitment of the Proteasome Complex into Dendritic Spines

Cited by 55 publications

References 53 publications

Roles of ubiquitination at the synapse

Roles of ubiquitination at the synapse

Regulation of the Proteasome by Neuronal Activity and Calcium/Calmodulin-dependent Protein Kinase II

Response of the Ubiquitin-Proteasome System to Memory Retrieval After Extended-Access Cocaine or Saline Self-Administration

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