Faculty Opinions recommendation of Synaptic protein degradation underlies destabilization of retrieved fear memory.

Author(s):  
Angus Nairn
Science ◽  
2008 ◽  
Vol 319 (5867) ◽  
pp. 1253-1256 ◽  
Author(s):  
S.-H. Lee ◽  
J.-H. Choi ◽  
N. Lee ◽  
H.-R. Lee ◽  
J.-I. Kim ◽  
...  

2009 ◽  
Vol 15 (5) ◽  
pp. 430-435 ◽  
Author(s):  
Bong-Kiun Kaang ◽  
Sue-Hyun Lee ◽  
Hyoung Kim

2021 ◽  
Vol 14 ◽  
Author(s):  
Kayla Farrell ◽  
Madeline Musaus ◽  
Shaghayegh Navabpour ◽  
Kiley Martin ◽  
W. Keith Ray ◽  
...  

Ubiquitin-proteasome mediated protein degradation has been widely implicated in fear memory formation in the amygdala. However, to date, the protein targets of the proteasome remain largely unknown, limiting our understanding of the functional significance for protein degradation in fear memory formation. Additionally, whether similar proteins are targeted by the proteasome between sexes has yet to be explored. Here, we combined a degradation-specific K48 Tandem Ubiquitin Binding Entity (TUBE) with liquid chromatography mass spectrometry (LC/MS) to identify the target substrates of the protein degradation process in the amygdala of male and female rats following contextual fear conditioning. We found that males (43) and females (77) differed in the total number of proteins that had significant changes in K48 polyubiquitin targeting in the amygdala following fear conditioning. Many of the identified proteins (106) had significantly reduced levels in the K48-purified samples 1 h after fear conditioning, suggesting active degradation of the substrate due to learning. Interestingly, only 3 proteins overlapped between sexes, suggesting that targets of the protein degradation process may be sex-specific. In females, many proteins with altered abundance in the K48-purified samples were involved in vesicle transport or are associated with microtubules. Conversely, in males, proteins involved in the cytoskeleton, ATP synthesis and cell signaling were found to have significantly altered abundance. Only 1 protein had an opposite directional change in abundance between sexes, LENG1, which was significantly enhanced in males while lower in females. This suggests a more rapid degradation of this protein in females during fear memory formation. Interestingly, GFAP, a critical component of astrocyte structure, was a target of K48 polyubiquitination in both males and females, indicating that protein degradation is likely occurring in astrocytes following fear conditioning. Western blot assays revealed reduced levels of these target substrates following fear conditioning in both sexes, confirming that the K48 polyubiquitin was targeting these proteins for degradation. Collectively, this study provides strong evidence that sex differences exist in the protein targets of the degradation process in the amygdala following fear conditioning and critical information regarding how ubiquitin-proteasome mediated protein degradation may contribute to fear memory formation in the brain.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 675 ◽  
Author(s):  
Laurie D. Cohen ◽  
Noam E. Ziv

Maintaining synaptic integrity and function depends on the continuous removal and degradation of aged or damaged proteins. Synaptic protein degradation has received considerable attention in the context of synaptic plasticity and growing interest in relation to neurodegenerative and other disorders. Conversely, less attention has been given to constitutive, ongoing synaptic protein degradation and the roles canonical degradation pathways play in these processes. Here we briefly review recent progress on this topic and new experimental approaches which have expedited such progress and highlight several emerging principles. These include the realization that synaptic proteins typically have unusually long lifetimes, as might be expected from the remote locations of most synaptic sites; the possibility that degradation pathways can change with time from synthesis, cellular context, and physiological input; and that degradation pathways, other than ubiquitin-proteasomal-mediated degradation, might play key roles in constitutive protein degradation at synaptic sites. Finally, we point to the importance of careful experimental design and sufficiently sensitive techniques for studying synaptic protein degradation, which bring into account their slow turnover rates and complex life cycles.


2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
B.-K. Kaang

An accumulating body of evidence shows that the retrieval process of long-term memory is not static and requires de novo protein synthesis. Thus long-term memories are dynamic and particularly become fragile during its retrieval. Importantly, memory retrieval is regarded as a step necessary for incorporating new information into preexisting memories. We have examined whether protein degradation is involved in the memory reorganization or not. In this presentation I will present the evidence that synaptic proteins are degraded by polyubiquitination and proteasome pathway in the hippocampus after the retrieval of contextual fear conditioning. In addition, we found that the infusion of a proteasome inhibitor into the hippocampus prevented the memory impairment induced by anisomycin, a protein synthesis inhibitor. This indicates that ubiquitin/proteasome-dependent protein degradation is involved in destabilization processes accompanying the memory retrieval. It also supports our hypothesis that preexisting memory is disrupted by synaptic protein degradation before updated memory is strengthened by protein synthesis. Our data also showed that synaptic protein degradation plays a critical role in fear memory extinction, a simple form of memory reorganization. Taken together, synaptic protein degradation is critically involved in the reorganization of the preexisting memories.


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