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。

基本信息

  • 批准号:
    16500236
  • 负责人:
  • 金额:
    $ 2.37万
  • 依托单位:
  • 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

项目摘要

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一员。SHPS-1的细胞质区域含有酪氨酸残基,酪氨酸残基被磷酸化,并与细胞质蛋白酪氨酸磷酸酶SHP-2结合。SHPS-1在大脑中高度表达,被认为在中枢神经系统中具有调节酪氨酸磷酸化信号的重要功能。SHPS-1的胞外区与其生理配体CD47特异性地相互作用。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一个细胞间通信系统(CD47-SHPS-1系统)。在本研究中,我们利用原代培养的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,前者主要分布在轴突上,后者主要分布在树突上。这些结果表明,CD47-SHPS-1系统在树突和轴突之间的相互作用部位起着定向细胞间信号系统的作用。我们还研究了CD47-SHPS-1系统在培养神经元中的功能。我们发现CD47的强制表达促进了神经突起的形成。我们还发现,含有SHPS-1胞外区的Fc融合蛋白可以诱导这些神经元形成丝状基座。此外,外源性表达的SHPS-1和CD47明显聚集在轴突和树突的扩大接触部位,每个轴突和树突都来自单独转染的神经元。我们的研究结果提示CD47-SHPS-1系统调节接触部位神经元的形态变化,从而调节神经元网络的形成。我们计划进一步研究CD47-SHPS-1系统在神经功能调节中的生理重要性。

项目成果

期刊论文数量(52)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
ブレインサイエンスレビュー2005
脑科学评论 2005
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Tanabe;S.;et.al.;Furue H et al.;古江 秀昌
  • 通讯作者:
    古江 秀昌
Negative regulation of phagocytosis in macrophages by the CD47-SHPS-1 system
  • DOI:
    10.4049/jimmunol.174.4.2004
  • 发表时间:
    2005-02-15
  • 期刊:
  • 影响因子:
    4.4
  • 作者:
    Okazawa, H;Motegi, SI;Matozaki, T
  • 通讯作者:
    Matozaki, T
Promotion of neurite and filopodium formation by CD47: Roles of integrins, Rac, and Cdc42
  • DOI:
    10.1091/mbc.e04-01-0019
  • 发表时间:
    2004-08-01
  • 期刊:
  • 影响因子:
    3.3
  • 作者:
    Miyashita, M;Ohnishi, 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 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。
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:
  • 影响因子:
    64.8
  • 作者:
    Koga, T;Inui, M;Takai, T
  • 通讯作者:
    Takai, T
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OHNISHI Hiroshi其他文献

Accumulation of dysregulated renal mononuclear phagocytes (rMoPh) and Th1 cells in the kidney of CD11c-specific Shp-1 knockout mice
CD11c 特异性 Shp-1 敲除小鼠肾脏中失调的肾单核吞噬细胞 (rMoPh) 和 Th1 细胞的积累
  • DOI:
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    0
  • 作者:
    WATANABE Mitsuharu;KANEKO Yoriaki;HIROMURA Keiju;KINOSHITA Masato;OHISHI Yuko;SAITO Yasuyuki;OHNISHI Hiroshi;MATOZAKI Takashi;NOJIMA Yoshihisa
  • 通讯作者:
    NOJIMA Yoshihisa
Dendritic cell-specific ablation of the protein tyrosine phosphatase Shp-1 induces autoimmune sialadenitis characterized by infiltration of CD4+ T cells and B cells
树突状细胞特异性去除蛋白酪氨酸磷酸酶Shp-1可诱导自身免疫性唾液腺炎,其特征是CD4 T细胞和B细胞浸润
  • DOI:
  • 发表时间:
    2017
  • 期刊:
  • 影响因子:
    0
  • 作者:
    KINOSHITA Masato;KANEKO Yoriaki;WATANABE Mitsuharu,OHISHI Yuko;SAITO Yasuyuki;OHNISHI Hiroshi;NOJIMA Yoshihisa;MATOZAKI Takashi;HIROMURA Keiju
  • 通讯作者:
    HIROMURA Keiju
Shp-1 in dendritic cells controls the development of memory-phenotype CD8+ T cells
树突状细胞中的 Shp-1 控制记忆表型 CD8 T 细胞的发育
  • DOI:
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    0
  • 作者:
    OHISHI Yuko;KANEKO Yoriaki;WATANABE Mitsuharu;KINOSHITA Masato;HIROMURA Keiju;SAITO Yasuyuki;OHNISHI Hiroshi;MATOZAKI Takashi;NOJIMA Yoshihisa
  • 通讯作者:
    NOJIMA Yoshihisa
Dendritic cell-specific ablation of the protein tyrosine phosphatase Shp1 induces enhanced production of inflammatory cytokines by toll-like receptor-mediated stimulation
树突状细胞特异性去除蛋白质酪氨酸磷酸酶Shp1,通过Toll样受体介导的刺激,诱导炎症细胞因子的产生增强
  • DOI:
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    0
  • 作者:
    OHISHI Yuko;KANEKO Yoriaki;WATANABE Mitsuharu;KINOSHITA Masato;HIROMURA Keiju;SAITO Yasuyuki;OHNISHI Hiroshi;MATOZAKI Takashi;NOJIMA Yoshihisa
  • 通讯作者:
    NOJIMA Yoshihisa

OHNISHI Hiroshi的其他文献

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{{ truncateString('OHNISHI Hiroshi', 18)}}的其他基金

Analysis of the signaling mechanisms that regulates brain stress responses through protein tyrosine phosphorylation
通过蛋白质酪氨酸磷酸化调节脑应激反应的信号机制分析
  • 批准号:
    23500437
  • 财政年份:
    2011
  • 资助金额:
    $ 2.37万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The role of visceral adipose tissue CD8+ T cells in obese murine asthma model
内脏脂肪组织CD8 T细胞在肥胖小鼠哮喘模型中的作用
  • 批准号:
    23591120
  • 财政年份:
    2011
  • 资助金额:
    $ 2.37万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Analysis of the role of a protein tyrosine phosphatase in regulation of neuronal functions
蛋白酪氨酸磷酸酶在神经元功能调节中的作用分析
  • 批准号:
    20500332
  • 财政年份:
    2008
  • 资助金额:
    $ 2.37万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Mathematical Modeling of the Marxian Economics Based on Neoclassical Growth Model
基于新古典增长模型的马克思经济学数学模型
  • 批准号:
    16530115
  • 财政年份:
    2004
  • 资助金额:
    $ 2.37万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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