Show simple item record

dc.contributor.authorVieuille, Christel Marieeng
dc.date.accessioned2012-08-09T11:47:24Z
dc.date.available2012-08-09T11:47:24Z
dc.date.issued2012-05-30eng
dc.date.submitted2012-05-30eng
dc.identifier.urihttp://hdl.handle.net/1956/5936
dc.description.abstractSynaptic plasticity is defined as the ability of a neuronal synapse to change in strength, and is believed to be the basis of learning and memory. An example of synaptic plasticity, by far the most studied, is long-term potentiation (LTP): a stable, activity-induced increase in synaptic efficacy. LTP requires de novo gene expression, protein synthesis and protein degradation. Transcriptional and post-transcriptional regulation controls new protein expression. In the past decade, small non-coding RNAs called microRNAs have emerged as key regulators of translation. MicroRNAs bind to target mRNAs by complementary binding and recruit a protein complex to mediate mRNA silencing. This complex is known as the microRNAinduced silencing complex (miRISC). The goals of this study were to investigate the composition of the miRISC in the rat dentate gyrus in vivo, to study modulation of the miRISC during LTP, and to uncover new candidate binding partners of Ago2. LTP was induced by HFS of the medial perforant path. The miRISC was isolated by immunoprecipitation of its core component, the protein Argonaute 2 (Ago2). Five proteins thought to bind Ago2 were analyzed by co-immunoprecipitation with Ago2. These proteins were GW182, the RNase III enzyme, Dicer, the RNA-binding protein, FMRP, and the RNA helicases, MOV10 and DDX6. DDX6 was the only protein found to be reliably associated with Ago2, even though all the proteins were detected in association with Ago2 in HEK cells expressing EGFP-Ago2. DDX6 was non-significantly dissociated from Ago2 during LTP. In the total lysate, none of the analyzed proteins were significantly modulated during LTP. Nevertheless, Argonaute 2 and GW182 were non-significantly upregulated, and MOV10 was non-significantly downregulated during LTP. The study does not show a significant remodeling of the miRISC during LTP, but neither does it exclude this possibility. Immunoprecipitated samples were analyzed by mass spectrometry. New candidate Ago2 binding partners were uncovered, such as the proteins DDX1 and FXR1, homologs of DDX6 and FMRP. A protein important for translation, poly-A-binding protein 1 (PABP1), was also detected.en
dc.format.extent1193170 byteseng
dc.format.mimetypeapplication/pdfeng
dc.language.isoengeng
dc.publisherThe University of Bergeneng
dc.subjectMicroRNAeng
dc.subjectHippocampuseng
dc.subjectArgonauteeng
dc.titleModulation of the Ago2-Associated microRNA Induced Silencing Complex during Long-Term Potentiation in the Rat Dentate Gyrus in Vivoeng
dc.typeMaster thesiseng
dc.type.degreeMaster i Medisinsk biologinob
dc.type.courseBMED395eng
dc.subject.nsiVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Neurology: 752eng
dc.subject.archivecodeMastergradeng
dc.subject.nus751910eng
dc.type.programMAMD-MEDBIeng
dc.rights.holderCopyright the author. All rights reserved


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record