Dissertation > Medicine, health > Basic Medical > Human Physiology > Neurophysiology > Nerve electrophysiology

The ubiquitin-proteasome -mediated protein degradation in synaptic plasticity in the hippocampal CA1 region

Author CaiFang
Tutor Thomas Behnisch
School Fudan University
Course Pharmacology
Keywords Ubiquitin-proteasome system Protein degradation Late long - term potentiation Synaptic input specificity Synaptic logo Synaptic heterologous go long term potentiation Dendritic spines The dendritic spines Rap specificity GTP activating protein Polo -like kinase 2 Hippocampal CA1 region Semliki Forest virus
CLC R338.8
Type PhD thesis
Year 2010
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Synaptic plasticity and use-dependent protein updated including the regulation of protein synthesis, degradation, transport and positioning in close contact. The combination of viral expression vector system, fluorescence imaging and electrophysiological studies ubiquitin-proteasome system (UPS)-mediated protein degradation in activity-dependent synaptic plasticity. Our main purpose is to (1) clear and synaptic plasticity in several major postsynaptic protein degradation in spatial and temporal order; (2) to understand the signaling cascades that UPS activation process included; (3) evaluation of a single tree Enter the degree of specificity; sudden spike level of protein degradation (4) clear these important synaptic protein degradation activity-dependent synaptic plasticity. In this study, the following major findings: UPS inhibitor MG132 inhibition of proteasome activity thereby undermining the advanced induction of LTP in hippocampal CA1 region, but does not affect the maintenance of late LTP. 2 late LTP induction after 10 minutes, and proteasome activity increased by about 50%; proteasome activity returned to control levels after 1 hour. In \Both'' Strong before Weak \early LTP could not continue as late LTP \The Weak \or calmodulin the phosphatase PP2B inhibitors cyclosporin A and MG132 perfusion can be mediated synaptic reversal MG132 heterologous go long-term increase. heterologous to another protein synthesis inhibitor anisomycin also inhibits MG132-mediated synaptic long-term potentiation. 5, L-LTP can be induced to increase the PP2B, PP1 activity; in \suppression, but PPl activity increase can not be applied MG132 blocked; the the phosphatase PP2B inhibitor completely abolished PP1 activity increase; the PP1 inhibitor MG132 joint applications can not be canceled synaptic heterologous to long-term potentiation. 6, successfully constructed forest virus vector containing eGFP fusion gene and SPAR Simon, Lick and directional transfected into rat hippocampal area years; compared with the expression of eGFP (1.26 spines / μm) pyramidal cells, expression of eGFP-SPAR (2.67 spines / μm) CA1 pyramidal cell dendritic spines were significantly increased. 7, tetanic stimulation induced LTP induced Plk2 mRNA transcription. 8, tetanic stimulation induced LTP SPAR fluorescence intensity decreases, reduced the SPAR fluorescence intensity proteasome inhibitors blocked SPAR degradation by the ubiquitin-proteasome system; protein synthesis inhibitors anisomycin and CDK5 inhibitor roscovitine can inhibit SPAR protein fluorescence intensity reduction, we speculate that protein synthesis inhibitors may inhibit Plk2 synthesis SPAR can not be phosphorylated and inhibit its degradation by UPS; CDK5 inhibitor, possibly through inhibition of the special sites SPAR protein phosphorylation, inhibit making Plk2 can not be combined with SPAR SPAR degradation., protein synthesis is inhibited, exclude laser quenching the role, SPAR protein fluorescence intensity is still decreased, the reduction in the intensity of this fluorescence may be combined of MG132 and NMDA receptor blocker APV blocking combined MG132 and roscovitine, and not be blocked by, presumably tetanic stimulation of protein synthesis was inhibited by activating NMDA receptors are involved in the SPAR protein degradation by the UPS, but this degradation is Plk-2 of 10 of the non-dependent protein synthesis inhibition, overexpression of eGFP-SPAR brain slices can still induce LTP, overexpression eGFP brain slices can not induce LTP, may inhibit the protein synthesis inhibitor Plk2 synthesis, SPAR can not be phosphorylated, and thus can not be by UPS degradation prompted SPAR in the induction of LTP play an important role.

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