Identification of novel target genes for the plasticity-related transcription factor Zif268.

摘要: Activity based alterations in synaptic connectivity are thought to underlie the processes involved learning and memory. Measurable changes neuronal activation by long-term potentiation (LTP) widely investigated as a possible cellular correlate of this phenomenon, it can be induced quickly elicit long-lasting modifications. These activity circuits sustained an altered pattern gene expression protein synthesis. The inducible transcription factor Zif268 has been implicated almost all models plasticity. Downstream targets zif268 believed contribute duration stabilisation NMDA receptor dependent LTP which, turn, linked various However, these downstream only just starting receive attention. By utilising wide range contemporary neuroscience techniques covering molecular & cell biology approaches, thesis proposes two known proteins, gephyrin ubiquilin, well novel (urma), potential Zif268. Both ubiquilin associated with GABAA receptors at inhibitory synapses. Gephyrin is cluster anchor postsynaptic sites whilst reported regulate surface expression. We found that mRNA levels were downregulated response increased transient transfection PC-12 cells stimulation primary cultured cortical neurones. In addition, also within same experimental paradigms, implying both transcriptional plasticity-related gene. A previously microarray experiment (James et al. 2005) contained 144 ESTs significantly affected compared control. Bioinformatic analyses tags revealed interesting genomic areas pertaining little published information. After further investigation, EST AI169020 transcript was treatment Additional data mining suggests urma may rarely expressed factor. Basal decreased knockout mouse, levels. Zif268 regulatory immediate early gene, activating or suppressing play role LTP. results indicate mediators receptor-dependent plasticity, modifying inhibitory-signalling. actively suppress factor, urma. findings important