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Related Concept Videos

The Proteasome01:13

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Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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Export of Misfolded Proteins out of the ER01:32

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After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
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The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
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Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
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Interplay between NMDA receptor dynamics and the synaptic proteasome.

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The European Journal of Neuroscience
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Synaptic proteasome activity is regulated by N-methyl-D-aspartate receptors (NMDARs). This study reveals that the GluN2B subunit of NMDARs specifically influences proteasome function and localization at excitatory synapses.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Synaptic Plasticity

Background:

  • Proteasome activity at excitatory synapses is crucial for neuronal communication.
  • Neuronal activity, particularly N-methyl-D-aspartate receptor (NMDAR) activation, mediates proteasome translocation to synapses.
  • NMDARs comprise various subunits influencing synaptic signaling and plasticity, but their specific role in proteasome interplay is unknown.

Purpose of the Study:

  • To investigate the specific interplay between proteasome and NMDAR subunits at the synapse.
  • To determine if NMDAR subunit composition affects proteasome dynamics and localization.

Main Methods:

  • Utilized single-molecule imaging and immunocytochemistry in rat hippocampal neurons.
  • Examined the effects of proteasome activation on NMDAR diffusion.
  • Assessed proteasome localization in response to altered GluN2B-NMDAR expression.

Main Results:

  • Sustained proteasome activation specifically enhances the lateral diffusion of GluN2B-containing NMDARs, but not GluN2A-NMDARs.
  • Downregulation of GluN2B-NMDAR expression leads to decreased proteasome localization at glutamatergic synapses.
  • Demonstrated a specific interaction between GluN2B-NMDARs and the synaptic proteasome.

Conclusions:

  • The cellular dynamics and synaptic localization of GluN2B-NMDARs and the proteasome are interconnected.
  • This interplay highlights a novel mechanism for NMDAR-dependent regulation of synaptic adaptation.
  • Findings shed light on subunit-specific regulation of synaptic plasticity.