Proteomic Analysis Reveals Sex-Specific Protein Degradation Targets in the Amygdala During Fear Memory Formation

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dc.contributor.authorFarrell, Kaylaen
dc.contributor.authorMusaus, Madelineen
dc.contributor.authorNavabpour, Shaghayeghen
dc.contributor.authorMartin, Kileyen
dc.contributor.authorRay, W. Keithen
dc.contributor.authorHelm, Richard F.en
dc.contributor.authorJarome, Timothy J.en
dc.date.accessioned2022-01-19T20:40:42Zen
dc.date.available2022-01-19T20:40:42Zen
dc.date.issued2021-09-29en
dc.date.updated2022-01-19T20:40:36Zen
dc.description.abstractUbiquitin-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.en
dc.description.versionPublished versionen
dc.format.extent16 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN 716284 (Article number)en
dc.identifier.doihttps://doi.org/10.3389/fnmol.2021.716284en
dc.identifier.eissn1662-5099en
dc.identifier.issn1662-5099en
dc.identifier.orcidJarome, Timothy [0000-0001-9189-8992]en
dc.identifier.orcidRay, William [0000-0002-1727-4994]en
dc.identifier.orcidHelm, Richard [0000-0001-5317-0925]en
dc.identifier.pmid34658783en
dc.identifier.urihttp://hdl.handle.net/10919/107791en
dc.identifier.volume14en
dc.language.isoenen
dc.publisherFrontiersen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000707263800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectLife Sciences & Biomedicineen
dc.subjectNeurosciencesen
dc.subjectNeurosciences & Neurologyen
dc.subjectubiquitinen
dc.subjectproteasomeen
dc.subjectamygdalaen
dc.subjectsex differenceen
dc.subjectMemoryen
dc.subjectconsolidationen
dc.subjectUBIQUITIN PROTEASOME SYSTEMen
dc.subjectRECOGNITIONen
dc.subjectPATHWAYen
dc.subject1103 Clinical Sciencesen
dc.subject1109 Neurosciencesen
dc.titleProteomic Analysis Reveals Sex-Specific Protein Degradation Targets in the Amygdala During Fear Memory Formationen
dc.title.serialFrontiers in Molecular Neuroscienceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2021-09-01en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Animal and Poultry Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Durelle Scotten

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