Developmental change in signal transduction regulating neurite outgrowth

调节神经突生长的信号转导的发育变化

• 批准号: 16500244
• 负责人: TAKEI Kohtaro
• 金额: $ 2.18万
• 依托单位: Yokohama City 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-16500244/
• 关键词: Neurite outgrowth; Signal transduction; Developmental change; Calcium; Growth cone; NCS-1; CALI

The aid of this study is to clarify signal transduction mechanisms regulating neurite outgrowth which show dynamic change in accordance with developmental process. Calcium acts important second messenger in the intracellular signal pathways in a variety of cell function. Intracellular calcium ion is strictly regulated and its optimal concentration is required for a proper neurite outgrowth. We first examined source of calcium for neurite outgrowth and calcium-dependent signaling in cultured dorsal root ganglion (DRG) neurons from early or late stages of chick embryos. In early developmental stages, calcium release from internal stores through inositol 1.4.5-trisphosphate (IP3) receptors was found to contribute on neurite outgrowth of chick DRG neuron, while calcium increases by influxes through plasma membrane and by release form internal stores through ryanodine receptors were found to be important for the neurite outgrowth. We next examined the calcium signal cascade regulating neuri … More te outgrowth in the early developmental stage. Neuronal calcium sensor-1 (NCS-1) is a high-affinity and low-capacity calcium binding protein that is specifically expressed in the nervous system. We found the clustering of NCS-1 in the growth cone that is located at a distal tip of neurite in chick DRG neurons. Immunocytochemistry revealed that NCS-1 was co-localized with type 1 IP3 receptor in the growth cone. Pharmacological inhibition of IP3 receptors decreased clustering distribution of NCS-1 in the growth cones and inhibited neurite outgrowth, but not affect growth cone morphology. Acute localized loss of NCS-1 function in the growth cone induced by chromophore-assisted laser inactivation (CALI) resulted in growth arrest of neurites and lamellipodial retraction, but not filopodial retraction. These findings suggest that calcium signaling mediated by NCS-1 in growth cone may regulate the intracellular calcium signaling regulating both of growth cone morphology and neurite outgrowth, and may functionally linked to InsP_3R1 in growth cone may promote neurite outgrowth in the earty developmental stages. Less

本研究的目的是阐明神经突起生长的信号转导机制，这些机制在发育过程中呈现动态变化。钙离子是细胞内多种信号传导途径中的重要第二信使，参与细胞的多种功能.细胞内钙离子受到严格的调控，其最佳浓度是神经突生长所必需的。我们首先研究了培养的早期或晚期鸡胚背根神经节（DRG）神经元突起生长和钙依赖性信号的钙源。在早期发育阶段，通过肌醇1.4.5-三磷酸（IP 3）受体从内部储存的钙释放被发现对鸡DRG神经元的突起生长有贡献，而钙通过质膜流入和通过兰尼碱受体从内部储存释放被发现对突起生长有重要作用。我们接下来检测了调节神经元钙信号级联反应， ...更多信息 在早期发育阶段的生长。神经元钙传感器-1（NCS-1）是一种高亲和力、低容量的钙结合蛋白，在神经系统中特异性表达。我们发现NCS-1在鸡DRG神经元的生长锥中聚集，生长锥位于神经突的远端。免疫细胞化学显示NCS-1与1型IP 3受体共定位于生长锥。药物抑制IP 3受体可减少NCS-1在生长锥中的聚集分布，抑制突起生长，但不影响生长锥的形态。发色团辅助激光灭活（卡利）诱导的生长锥中NCS-1功能的急性局部丧失导致神经突生长停滞和板状伪足退缩，但不导致丝状伪足退缩。这些结果表明，生长锥中NCS-1介导的钙信号可能通过调节细胞内钙信号来调节生长锥的形态和突起的生长，并可能与生长锥中的InsP_3R1功能相关，从而促进早期发育阶段的突起生长。少

项目成果

FKBP133 : A novel mouse FK-506 binding protein homolog alters growth conmorphology

FKBP133：一种新型小鼠 FK-506 结合蛋白同源物改变生长形态

• 期刊: Biochem. Biophys. Res. Comm. (印刷中)
• 作者: Nakajima;O.;Nakamura;F.;Yamashita;N.;Tomita;Y.;Syto;F.;Okada;T.;Iwamattsu;A.;Kondo;E.;Fujisawa;H.;Takei;K.;Goshima;Y.
• 通讯作者: Y.

Cdk5 and GSKβ sequentiaaly phosphorylate CRMP2 in Semaphorin-3A signaling : Implication of common phosphorylating mechanism underlyin axon guidance and Alzheimer disease

Cdk5 和 GSKβ 在 Semaphorin-3A 信号传导中依次磷酸化 CRMP2 ：轴突引导和阿尔茨海默病的常见磷酸化机制的含义

• 发表时间: 2005
• 期刊: Genes to Cells 10
• 作者: Uchida;Y.;Ohshima;T.;Sasaki;Y.;Suzuki;H.;Yanai;S.;Yamashita;N.;Nakamura;F.;Takei;K.;Ihara;Y.;Mikoshiba;K.;Kolattukudy;P.;Honnorat;J.;Goshima;Y.
• 通讯作者: Y.

Cdk5 and GSKβ sequentially phosphorylate CRMP2 in Semaphorin-3A signaling : Implication of common phosphorylating mechanism underlying axon guidance and Alzheimer disease

Cdk5 和 GSKβ 在 Semaphorin-3A 信号传导中依次磷酸化 CRMP2：轴突引导和阿尔茨海默病潜在的常见磷酸化机制的含义

• 发表时间: 2005
• 期刊: Genes to Cells 10
• 作者: Uchida;Y.;Ohshima;T.;Sasaki;Y.;Suzuki;H.;Yanai;S.;Yamashita;N.;Nakamura;F.;Takei;K.;Ihara;Y.;Mikoshiba;K.;Kolattukudy;P.;Honnorat;J.;Goshima;Y.
• 通讯作者: Y.

Regulation of dendritic branching and spine maturation by semaphorin3A-fyn signaling

• DOI: 10.1523/jneurosci.5453-05.2006
• 发表时间: 2006-03-15
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Morita, A;Yamashita, N;Goshima, Y
• 通讯作者: Goshima, Y

Correlation between Sema3A-induced facilitation of axonal transport an local activation of a translation initiation factor eIF-4E

Sema3A 诱导的轴突运输促进与翻译起始因子 eIF-4E 局部激活之间的相关性

• 发表时间: 2004
• 期刊: Journal of Neuroscience 24
• 作者: Li;C.;Sasaki;Y.;Takei;K.;Yamamoto;H.;Shouji;M.;Sugiyama;Y.;Kawakami;T.;Nakamura;F.;Yagi;T.;Ohshima;T.;Goshima;Y.
• 通讯作者: Y.