Proline Rich 7 (Prr7): An NMDA Receptor-Associated Synapto-Nuclear Protein Messenger in Control of c-Jun-Dependent Gene Transcription?

大脑中长期记忆的形成需要基因表达的调节。在神经元中，不同的机制已经进化到将突触活动与基因转录耦合。其中一些信号机制需要将蛋白质从突触转运到细胞核。突触核蛋白信使的一个特别丰富的来源是N-甲基-D-天冬氨酸受体（NMDAR）复合物。NMDAR是神经元可塑性的重要介质，其数量和在突触处的定位受到严格调节。基于以前和最近未发表的工作，我们建议研究跨膜衔接蛋白Prr 7的神经元功能，该蛋白直接与NMDAR相关，并似乎调节其表面表达。增强突触活性后，Prr 7易位到细胞核，并可以结合转录因子c-Jun. With this application，we want to prove the hypothesis that Prr 7 can serve as a assistant subunit of NMDAR and that after proteolytical cleavage a fragment of the protein is active transported to the nucleus，where it then regulates c-Jun-dependent gene transcription.我们将分析这种新的信号机制的基因组反应。最后，我们将测试切割的Prr 7的核输入提供表面表达和活化的NMDAR的数量的读出的想法。

The formation of long-term memories in the brain requires regulation of gene expression. In neurons different mechanisms have evolved to couple synaptic activity to gene transcription. Some of these signaling mechanisms need the transport of proteins from synapses to the nucleus. A particular rich source of synapto-nuclear protein messengers is the N-Methyl-D-Aspartate-receptor (NMDAR) complex. NMDAR are crucial mediators of neuronal plasticity and their number and localization at synapses is tightly regulated. Based on previous and recent unpublished work we propose to study the neuronal function of the transmembrane adaptor protein Prr7, which directly associates with NMDAR and appears to regulate their surface expression. Following enhanced synaptic activity Prr7 translocates to the nucleus and can bind the transcription factor c-Jun. With this application we want to prove the hypothesis that Prr7 can serve as an auxiliary subunit of NMDAR and that after proteolytical cleavage a fragment of the protein is actively transported to the nucleus, where it then regulates c-Jun-dependent gene transcription. We will analyze the genomic response to this novel signaling mechanism. Finally, we will test the idea that the nuclear import of cleaved Prr7 provides a read-out of the number of surface expressed and activated NMDAR.