Activity-dependent dynamics and sequestration of proteasomes in dendritic spines
Abstract
The regulated degradation of proteins by the ubiquitin proteasome pathway is emerging as an important modulator of synaptic function and plasticity. The proteasome is a large, multi-subunit cellular machine that recognizes, unfolds and degrades target polyubiquitinated proteins. Here we report NMDA (N-methyl-D-aspartate) receptor-dependent redistribution of proteasomes from dendritic shafts to synaptic spines upon synaptic stimulation, providing a mechanism for local protein degradation. Using a proteasome-activity reporter and local perfusion, we show that synaptic stimulation regulates proteasome activity locally in the dendrites. We used restricted photobleaching of individual spines and dendritic shafts to reveal the dynamics that underlie proteasome sequestration, and show that activity modestly enhances the entry rate of proteasomes into spines while dramatically reducing their exit rate. Proteasome sequestration is persistent, reflecting an association with the actin-based cytoskeleton. Together, our data indicate that synaptic activity can promote the recruitment and sequestration of proteasomes to locally remodel the protein composition of synapses.
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Rpt6 S120 is targeted by CaMKII.
“this site is targeted by the plasticity-related kinase Ca2+/calmodulin-dependent kinase II (CaMKII)”
From Altered Phosphorylation of the Proteasome Subunit Rpt6 Has Minimal Impact on Synaptic Plasticity and Learning (2021) · cites this paper as Bingol and Schuman, 2006
The 26S proteasome may play an instructive role at synapses, with activity-dependent and NMDA receptor-dependent translocation and sequestration of proteasomes at synapses.
“In 2006, Bingol and Schuman provided the first evidence that the 26S proteasome may play an instructive role at synapses in work that described the activity-dependent and NMDA receptor-dependent translocation and sequestration of proteasomes at synapses (Bingol and Schuman, 2006).”
From Altered Phosphorylation of the Proteasome Subunit Rpt6 Has Minimal Impact on Synaptic Plasticity and Learning (2021) · cites this paper as Bingol and Schuman, 2006
CaMKIIα stimulates proteasome peptidase activity through activity-dependent phosphorylation of serine 120 (S120) on Rpt6.
“CaMKIIα also stimulates proteasome peptidase activity through activity-dependent phosphorylation of serine 120 (S120) on Rpt6, an ATPase subunit on the 19S RP of the proteasome (Bingol and Schuman, 2006; Djakovic et al., 2009, 2012; Bingol et al., 2010).”
From Altered Phosphorylation of the Proteasome Subunit Rpt6 Has Minimal Impact on Synaptic Plasticity and Learning (2021) · cites this paper as Bingol and Schuman, 2006
The degradation of PSD proteins via the ubiquitin-proteasome system also sculpts the PSD structure and plays a primary role in synaptic plasticity.
“The degradation of PSD proteins via the ubiquitin-proteasome system (Bingol and Schuman, 2006) also sculpts the PSD structure and plays a primary role in synaptic plasticity.”
From Human Brain/Cloud Interface (2019) · cites this paper as Bingol and Schuman, 2006
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References 31 · Cited by 347
- Authors
- Bingol, B., & Schuman, E. M.
- Affiliations
- California Institute of Technology (US)
- Corresponding author
- Schuman, Erin M.
- Venue
- Nature
- Published
- 2006-06
- Volume
- 441
- Issue
- 7097
- Pages
- 1144-1148
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2038719756
- Cited by
- 347
- References
- 31
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 14 · 2023: 11 · 2022: 23 · 2021: 26 · 2020: 12 · 2019: 11 · 2018: 17 · 2017: 21 · 2016: 20 · 2015: 17 · 2014: 18 · 2013: 17 · 2012: 15
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- proteasome, dendritic spines, ubiquitin-proteasome system, NMDA receptor, synaptic plasticity, actin cytoskeleton
- MeSH terms
- Actins, Animals, Cells, Cultured, Cytoskeleton, Hippocampus, Potassium Chloride, Protein Binding, Synapses, Receptors, N-Methyl-D-Aspartate, Photobleaching, Proteasome Endopeptidase Complex, Dendritic Spines, Rats
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