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

这项研究的帮助是阐明调节神经落生的信号转导机制，该机制根据发育过程显示了动态变化。钙在各种细胞功能的细胞内信号途径中起重要的第二信使。细胞内钙离子受到严格调节，并且其最佳浓度是正确的神经产物生长所必需的。我们首先检查了来自雏鸡胚胎的早期或晚期培养的背根神经神经元（DRG）神经元中神经蛋白神经产物和钙依赖性信号传导的钙来源。在早期发育阶段，发现从内部商店到肌醇1.4.5-三磷酸（IP3）受体的钙释放会导致Chick DRG神经元的神经蛋白神经产物的生长，而钙通过质膜的影响而增加，并且通过释放形式的内部商店通过RyanoNodine受体释放出来，发现了重要的。接下来，我们检查了钙信号级联调节神经……在早期发育阶段的进一步生长。神经元钙传感器-1（NCS-1）是一种在神经系统中特异性表达的高亲和力和低容量钙结合蛋白。我们发现NCS-1在雏鸡DRG神经元中神经蛋白远端的生长锥中的聚类。免疫细胞化学表明，NCS-1与生长锥中的1型IP3受体共定位。 IP3受体的药理抑制作用降低了NCS-1在生长锥中的聚类分布，并抑制了神经元的产物，但不会影响生长锥形态。发色团辅助激光失活引起的生长锥中NCS-1功能的急性局部损失导致神经膜的生长停滞和片状膜片缩回，但没有丝状恢复。这些发现表明，由NCS-1在生长锥中介导的钙信号传导可能调节生长锥形态和神经元的生长的细胞内钙信号传导调节，并且可能与生长锥中的Insp_3R1在功能上有联系，可能会促进eary发育阶段的神经元阳性。较少的

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.