Role of IP_3 receptor/ Ca^<2+> signaling for synaptic plasticity and development and differentiation of brain

IP_3受体/Ca^2信号对突触可塑性和大脑发育分化的作用

• 批准号: 13308044
• 负责人: MIKOSHIBA Katsuhiko
• 金额: $ 29.2万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13308044/
• 关键词: dorsoventral axis formation; IP_3 receptor; GSK3β; NF-AT; Calcium; Wnt singnaling; カルシウムシグナリング; 神経可塑性; 脳の発生・分化; シナプス; 長期増強; 長期抑圧; IP_3レセプター欠損マウス

The involvement of IP_3-Ca^<2+> signaling in dorsoventral axis formation in Xenopus embryo has been proposed, but the immediate target of free Ca^<2+> is not well understood. The secreted Wnt protein family comprises two functional groups, canonical Wnt and Wnt/Ca^<2+> pathways. Despite the finding that the Wnt/Ca^<2+> pathway interfered with the canonical Wnt pathway, the underlying molecular mechanism is poorly understood. We cloned the cDNA encoding Xenopus homolog of the nuclear factor of activated T-cell (XNF-AT). Gain-of-function XNF-AT mutant (CA XNF-AT) inhibited anterior development of the primary axis as well as Xwnt8-induced ectopic dorsal axis. Loss-of-function XNF-AT mutant (DN XNF-AT) induced an ectopic dorsal axis and expression of the canonical Wnt signaling target molecules, siamois and Xnr3. Xwnt5A induced translocation of XNF-AT from the cytosol to the nucleus. These data strongly suggest that XNF-AT functions as a downstream target of Wnt/Ca^<2+> and IP_3-Ca^<2+> pathways and plays an essential role in mediating ventral signals in the Xenopus embryo by suppressing the canonical Wnt pathway.

已提出IP_3-Ca ^ 2+ 信号传导参与爪蟾胚胎背腹轴形成，但游离Ca ^ 2+ 的直接靶标尚不清楚。分泌的Wnt蛋白家族包含两个功能组，典型Wnt和Wnt/Ca 2+ 途径。尽管发现Wnt/Ca ^ 2+ 途径干扰经典Wnt途径，但其潜在的分子机制仍知之甚少。我们克隆了编码激活 T 细胞核因子 (XNF-AT) 的非洲爪蟾同源物的 cDNA。功能获得性 XNF-AT 突变体 (CA XNF-AT) 抑制主轴的前部发育以及 Xwnt8 诱导的异位背轴。功能丧失的 XNF-AT 突变体 (DN XNF-AT) 诱导异位背轴和经典 Wnt 信号传导靶分子 siamois 和 Xnr3 的表达。 Xwnt5A 诱导 XNF-AT 从细胞质易位到细胞核。这些数据强烈表明XNF-AT作为Wnt/Ca ^ 2+ 和IP_3-Ca ^ 2+ 途径的下游靶标起作用，并且通过抑制经典Wnt途径在介导非洲爪蟾胚胎中的腹侧信号中发挥重要作用。

项目成果

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