Study of IP_3 receptor/Ca^<2+> signaling in neural plasticity and brain development and differentiation

IP_3受体/Ca^2信号在神经可塑性和脑发育分化中的研究

• 批准号: 20220007
• 负责人: MIKOSHIBA Katsuhiko
• 金额: $ 132.87万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20220007/
• 关键词: 神経伝達物質; 受容体; IP_3; カルシウム振動; 小胞体ストレス; グリア細胞; 自己免疫疾患; 心疾患; IRBIT; IP3受容体; 神経可塑性; カルシウムイオン; トランスグルタミナーゼ; アストロサイト; IP_3受容体; シナプス可塑性; カルシウムイオンチャネル; マクロピノサイトーシス; 成長円錐の退縮; 記憶・学習; チャネルの開口メカニズム; カルシウムイオンセンサー; 心臓形態形成; アルツハイマー病; ハンチントン病; GAB

IP_3 is important in cell signaling but requires the IP_3 receptor (IP_3R) to mediate all of its effects. Structural and biochemical studies indicate that the IP_3R provides a platform for molecules to interact, and combinations of associated molecules results which we discovered such as ERp44, GRP78, 80K-H et al, in functional diversity of cell signaling. IP_3Rs determine the trajectory of cell signaling by working as a signaling hub for interaction with differential molecular complexes which we discovered for various cell functions. The IP_3R signaling trajectory, in turn, plays a crucial role in cellular functions, in addition, IRBIT which is released from IP_3R as 3^<rd> messenger, also plays a variety of role. The abnormality of IP_3R signaling results in diseases such as neuronal degeneration, learning deficient, cardiogenesis abnormality, osteoporosis, auto-immune-disease, acute pancreatitis. We have developed ultra-sensitive genetically encoded Ca^<2+> indicator, Ca^<2+> pump indicator and established in vivo imaging of the cerebellum and cerebral cortex by two photon microscopy to study more in detail.

IP_3 在细胞信号传导中很重要，但需要 IP_3 受体 (IP_3R) 来介导其所有作用。结构和生化研究表明，IP_3R 为分子相互作用提供了一个平台，我们发现 ERp44、GRP78、80K-H 等相关分子的组合导致细胞信号传导的功能多样性。 IP_3R 作为信号中枢与我们发现的各种细胞功能的差异分子复合物相互作用，从而确定细胞信号传导的轨迹。反过来，IP_3R信号轨迹在细胞功能中起着至关重要的作用，此外，从IP_3R释放的IRBIT作为第3^<rd>信使，也发挥着多种作用。 IP_3R信号异常会导致神经元变性、学习障碍、心脏生成异常、骨质疏松、自身免疫性疾病、急性胰腺炎等疾病。我们开发了超灵敏的基因编码Ca^2+指示剂、Ca^2+泵指示剂，并通过两个光子显微镜建立了小脑和大脑皮层的体内成像，以进行更详细的研究。

项目成果

Zic deficiency in the cortical marginal zone and meninges results in cortical lamination defects resembling those in type II lissencephaly

• DOI: 10.1523/jneurosci.5735-07.2008
• 发表时间: 2008-04-30
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Inoue, Takashi;Ogawa, Masaharu;Aruga, Jun
• 通讯作者: Aruga, Jun

Neuronal overexpression of IP3 receptor 2 is detrimental in mutant SOD1 mice

IP3 受体 2 的神经元过度表达对突变 SOD1 小鼠有害

• DOI: 10.1016/j.bbrc.2012.10.094
• 发表时间: 2012
• 期刊: Biochem Biophys Res Commun.
• 作者: D. Kulic;W. Takano and Y. Nakamura;酒井邦嘉;Staats KA
• 通讯作者: Staats KA

The Discovery of the IP3 Receptor

IP3受体的发现

• DOI: 10.1166/msr.2012.1009
• 发表时间: 2012
• 期刊: Messenger
• 作者: Hatanaka N;Tokuno H;Nambu A;Takada M;神永拓,安藤雄太,大月智史,小田中浩平,中村仁彦;明和政子;Mikoshiba K.
• 通讯作者: Mikoshiba K.

CD spectra show the relational style between Zic-, Gli-, Glis-zinc finger protein and DNA

• DOI: 10.1016/j.bbapap.2008.01.013
• 发表时间: 2008-07-01
• 期刊: BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
• 影响因子: 3.2
• 作者: Sakai-Kato, Kumiko;Ishiguro, Akira;Utsunomiya-Tate, Naoko
• 通讯作者: Utsunomiya-Tate, Naoko

Receptor-Selective Diffusion Barrier Enhances Sensitivity of Astrocytic Processes to Metabotropic Glutamate Receptor Stimulation

• DOI: 10.1126/scisignal.2002498
• 发表时间: 2012-04-03
• 期刊: SCIENCE SIGNALING
• 影响因子: 7.3
• 作者: Arizono, Misa;Bannai, Hiroko;Mikoshiba, Katsuhiko
• 通讯作者: Mikoshiba, Katsuhiko