Analysis of protein tyrosine phosphorylation signal, which regulates synaptic function.

分析调节突触功能的蛋白质酪氨酸磷酸化信号。

• 批准号: 16500236
• 负责人: OHNISHI Hiroshi
• 金额: $ 2.37万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16500236/
• 关键词: Protein tyrosine phosphorylation; Intercellular communication; Axon; Dendrite; Neuronal network; Neuronal morphology; SHPS-1; CD47; 神経栄養因子; 神経軸策; 神経シナプス; 神経回路網

SHPS-1 (SHP substrate-1) is a member of immunoglobulin superfamily membrane proteins. Cytoplasmic region of SHPS-1 contains tyrosine residues, which are phosphorylated and binds to a cytplasmic protein tyrosine phosphatase, SHP-2. SHPS-1 is highly expressed in the brain, and thought to have an important function to regulate tyrosine phosphorylation signal in the central nervous system. Extracellular region of SHPS-1 specifically interacts with its physiological ligand, CD47. CD47 is also an immunoglobulin superfamily membrane protein. This interaction between CD47 and SHPS-1 constitutes an intercellular communication system (the CD47-SHPS-1 system). In this research, we analyzed expression patterns of these two molecules by using primary cultured hippocampal neurons, and we found that SHPS-1 and CD47 were localized in a different manner; the former was predominantly on axons and the latter on dendrites, respectively. These results suggest that the CD47-SHPS-1 system acts as a directional intercellular signaling system at the interaction sites between dendrites and axons. We have also investigated the function of the CD47-SHPS-1 system in cultured neurons. We found that forced expression of CD47 promoted neurite formation. We also found that an Fc fusion protein containing the extracellular region of SHPS-1 induced filopodium formation in these neurons. Furthermore, exogenously expressed SHPS-1 and CD47 were markedly accumulated at the enlarged contact sites of axon and dendrite, each of which was derived from neurons transfected separately. All our findings suggest the CD47-SHPS-1 system regulates morphological change of neurons at their contact site, thereby regulates neuronal network formation. We are planning to further investigate the physiological importance of the CD47-SHPS-1 system in the regulation of neuronal function.

SHPS-1（SHP底物1）是免疫球蛋白超家族膜蛋白的成员。 SHPS-1的细胞质区域含有酪氨酸残基，酪氨酸残基被磷酸化并与细胞质量蛋白酪氨酸磷酸酶SHP-2结合。 SHPS-1在大脑中高度表达，并被认为具有调节中枢神经系统中酪氨酸磷酸化信号的重要功能。 SHPS-1的细胞外区域特异性与其生理配体CD47相互作用。 CD47也是一种免疫球蛋白超家族膜蛋白。 CD47和SHPS-1之间的这种相互作用构成了细胞间通信系统（CD47-SHPS-1系统）。在这项研究中，我们通过使用原发性海马神经元分析了这两个分子的表达模式，我们发现SHPS-1和CD47以不同的方式定位。前者主要是在轴突上，后者分别在树突上。这些结果表明，在树突和轴突之间的相互作用位点，CD47-SHPS-1系统充当方向的细胞间信号系统。我们还研究了CD47-SHPS-1系统在培养的神经元中的功能。我们发现CD47强迫表达促进了神经突的形成。我们还发现，含有SHPS-1的细胞外区域的FC融合蛋白在这些神经元中诱导的丝状降膜形成。此外，在轴突和树突的扩大接触部位明显积累了外源表达的SHPS-1和CD47，每个接触位点是分别转染的神经元的。我们所有的发现都表明，CD47-SHPS-1系统调节神经元在其接触位点的形态变化，从而调节神经元网络形成。我们计划进一步研究CD47-SHPS-1系统在调节神经元功能中的生理重要性。

项目成果

Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis

• DOI: 10.1038/nature02444
• 发表时间: 2004-04-15
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Koga, T;Inui, M;Takai, T
• 通讯作者: Takai, T

Differential localization of SH2 domain-containing protein tyrosine phosphatase substrate-1 and CD47 and its molecular mechanism in cultured hippocampal neurons.

含SH2结构域的蛋白酪氨酸磷酸酶底物-1和CD47在培养海马神经元中的差异定位及其分子机制。

• 发表时间: 2005
• 期刊: The Journal of Neuroscience 25巻・10号
• 作者: Ohnishi;H. et al.
• 通讯作者: H. et al.

Ectodomain shedding of SHPS-1 and its role in regulation of cell migration

• DOI: 10.1074/jbc.m313085200
• 发表时间: 2004-07-02
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Ohnishi, H;Kobayashi, H;Matozaki, T
• 通讯作者: Matozaki, T

Differential localization of SH2 domain-containing protein tyrosine phosphatase substrate-1 and CD47 and its molecular mechanism in cultured hipnocampal neurons

培养海马神经元中SH2结构域蛋白酪氨酸磷酸酶底物1和CD47的差异定位及其分子机制

• 发表时间: 2005
• 期刊: The Journal of Neuroscience 25巻・10号
• 作者: Ohnishi;H. et al.
• 通讯作者: H. et al.

神経化学44巻4号

神经化学第 44 卷，第 4 期

• 发表时间: 2005
• 作者: Iwasaki Y;Yoshida M;Hattori M;Hashizume Y;Sobue G.;大西浩史 ら
• 通讯作者: 大西浩史 ら