Molecular mechanism of effect of secreted active neuropsin on neighboring synapses
分泌的活性神经蛋白酶对邻近突触影响的分子机制
基本信息
- 批准号:22700396
- 负责人:
- 金额:$ 2.58万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Young Scientists (B)
- 财政年份:2010
- 资助国家:日本
- 起止时间:2010 至 2011
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Protease-mediated signaling is an important modulator of the nervous system. However, identifying the specific signaling substrates of such proteases is limited by the rapidity with which intermediate substrate forms are cleaved and released. Here, a screening method to detect non-cleaved enzyme-bound forms was developed and used to identify a novel neuropsin/neuregulin-1(NRG-1) proteolytic signaling system, which is specifically localized in microdomain of synaptic cleft. The extracellular protease, neuropsin, cleaved mature NRG-1(comprising the NRG-1 extracellular domain) at three newly-identified sites to remove the NRG-1 heparin-binding domain. This released the ligand moiety from the matrix-glycosaminoglycan pool and enabled it to phosphorylate the NRG-1 receptor, p185(ErbB4). Thus, processed-NRG-1-ErbB4 signaling contributes to the modulation of early-phase long-term potentiation of Schaffer collaterals. This signaling system may be important for both animal and human cognition, and its dysfunction may contribute to human mental disorders such as schizophrenia and bipolar disorder.
蛋白酶介导的信号传导是神经系统的重要调节剂。然而,鉴定这类蛋白酶的特异性信号传导底物受到中间底物形式被切割和释放的快速性的限制。在这里,一种筛选方法来检测非切割的酶结合形式的开发和使用,以确定一种新的neuropsin/neuregulin-1(NRG-1)的蛋白水解信号系统,这是专门定位于突触间隙的微域。细胞外蛋白酶neuropsin在三个新鉴定的位点切割成熟NRG-1(包含NRG-1细胞外结构域),以去除NRG-1肝素结合结构域。这从基质-糖胺聚糖池中释放出配体部分,使其能够磷酸化NRG-1受体p185(ErbB 4)。因此,加工的NRG-1-ErbB 4信号有助于调节Schaffer侧支的早期长时程增强。这个信号系统可能对动物和人类的认知都很重要,它的功能障碍可能导致人类精神障碍,如精神分裂症和双相情感障碍。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Neuropsin dependent synaptic tagging in mouse hippocampus
小鼠海马神经蛋白酶依赖性突触标记
- DOI:
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:ISHIKAWA;Y.;TAMURA;H. & SHIOSAKA;S
- 通讯作者:S
Diversity of Neuropsin(Kallikrein8)-dependent Synaptic Associativity in the Hippocampal Pyramidal Neuron
海马锥体神经元神经蛋白酶 (Kallikrein8) 依赖性突触关联性的多样性
- DOI:
- 发表时间:2011
- 期刊:
- 影响因子:0
- 作者:ISHIKAWA;Y.;TAMURA;H. & SHIOSAKA;S
- 通讯作者:S
Diversity of neuropsin-dependent synaptic assocativity
神经蛋白酶依赖性突触关联性的多样性
- DOI:
- 发表时间:2011
- 期刊:
- 影响因子:0
- 作者:Ishikawa Y;Tamura H and Shiosaka S
- 通讯作者:Tamura H and Shiosaka S
Functional neuroimaging by using implantable CMOS multimodal device in freely-moving mouse. Pros
使用植入式 CMOS 多模态设备对自由移动的小鼠进行功能神经成像。
- DOI:
- 发表时间:2011
- 期刊:
- 影响因子:0
- 作者:Kobayashi T;Tamura H;Hatanaka Y;Motoyama M;Noda T;Sasagawa K;Tokuda T;Ishikawa Y;Shiosaka S and Ohta J
- 通讯作者:Shiosaka S and Ohta J
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TAMURA Hideki其他文献
TAMURA Hideki的其他文献
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{{ truncateString('TAMURA Hideki', 18)}}的其他基金
Processing of cell adhesion molecule L1 via neuropsin
通过神经蛋白酶处理细胞粘附分子 L1
- 批准号:
19700342 - 财政年份:2007
- 资助金额:
$ 2.58万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
A study on monolithic vibrational gyrosensor to detect triaxial angular velocities
单片振动陀螺传感器三轴角速度检测研究
- 批准号:
18760050 - 财政年份:2006
- 资助金额:
$ 2.58万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Construction and application of a small-sized spray apparatus utilizing electrothermal explosion of spray powders to a study on the production of refractory spray coatings
小型电热爆炸喷涂装置的构建及其在耐火喷涂层生产中的应用研究
- 批准号:
08555169 - 财政年份:1996
- 资助金额:
$ 2.58万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Study on the synthesis of Spray Coating Composed of Refractory Boride Ceramics by Electrothermal Explosion of powders
粉末电热爆炸合成耐火硼化物陶瓷喷涂层的研究
- 批准号:
07805066 - 财政年份:1995
- 资助金额:
$ 2.58万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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