Analysis of a Novel Protein Shootin1, which is involved in organization of an asymmetric signal for neuronal polarization

新型蛋白质 Shootin1 的分析，该蛋白质参与神经元极化不对称信号的组织

• 批准号: 18300107
• 负责人: INAGAKI Naoyuki
• 金额: $ 10.98万
• 依托单位: Nara Institute of Science and Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18300107/
• 关键词: Neuron; Cell polarity; Axon; Dendrite; Shootin1; L1; Actin; Growth cone; Shootin1; Wave; PI 3-kinase; ノックアウトマウス

The basic function of neurons is to receive, integrate and transmit signals. To do so, most neurons develop polarity by forming a single axon and multiple dendrites. Neurons have the remarkable ability to polarize even in symmetrical in vitro environments. Although recent studies have shown that asymmetric intracellular signals can induce neuronal polarization, it remains unclear how these polarized signals are organized without asymmetric cues. We recently described an intracellular protein, shootin1, which plays a critical role in neuronal polarization. During the symmetry breaking step, shootin1 becomes up-regulated, undergoes a fluctuating accumulation in growth cones at neurite tips, and eventually accumulates asymmetrically in a single growth cone. Accumulation of shootin1 in nerve growth cones also enhanced neurite elongation. In this study, we examined molecular mechanisms for shootin1-induced neurite outgrowth and the mechanisms for generation of asymmetric signal of shootin1. Shootin1 not only acted as a upstream regulator of PI 3-kinase but also enhanced neurite elongation, by linking a cell adhesion molecule Ll-CAM to actin filament retrograde flow as a "clutch molecule". We also obtained data to suggest that positive feedback amplification of shootin1 signal in growth cones contributes to generation of asymmetric shootin 1 signals during neuronal polarization. We also succeeded in generation of shootin 1 knockout mice, and are currently analyzing their phenotypes.

神经元的基本功能是接收、整合和传输信号。为此，大多数神经元通过形成单个轴突和多个树突来发展极性。即使在对称的体外环境中，神经元也具有非凡的能力。虽然最近的研究表明，不对称的细胞内信号可以诱导神经元极化，但仍然不清楚这些极化信号是如何组织没有不对称的线索。我们最近描述了一种细胞内蛋白，shootin 1，它在神经元极化中起着关键作用。在对称性破坏步骤中，shootin 1被上调，在神经突尖端的生长锥中经历波动的积累，并最终在单个生长锥中不对称地积累。shootin 1在神经生长锥中的积累也促进了神经突起的伸长。在这项研究中，我们研究的分子机制shootin 1诱导的轴突生长和shootin 1的不对称信号的产生机制。Shootin 1不仅作为PI 3-激酶的上游调节因子，而且通过将细胞粘附分子L1-CAM作为“离合器分子”连接到肌动蛋白丝逆行流上而促进神经突起的伸长。我们还获得的数据表明，shootin 1信号的正反馈放大在生长锥有助于产生不对称shootin 1信号在神经元极化。我们还成功地产生了shootin 1基因敲除小鼠，目前正在分析它们的表型。

项目成果

Shootin1 interacts with actin retrograde flow and L1-CAM to promote axon outgrowth.

• DOI: 10.1083/jcb.200712138
• 发表时间: 2008-06-02
• 期刊: The Journal of cell biology
• 作者: Shimada T;Toriyama M;Uemura K;Kamiguchi H;Sugiura T;Watanabe N;Inagaki N
• 通讯作者: Inagaki N

Neuronal polarity formation by feedback interaction between shoootin1 and neurite length

Shoootin1 和神经突长度之间的反馈相互作用形成神经元极性

• 发表时间: 2007
• 作者: Toriyama;M.;Sakumura;Y.;Asano;T.;Shimada;T.;Inagaki;N
• 通讯作者: N

Neuronal symmetry breaking and polarity formation by shoootin1

Shoootin1 破坏神经元对称性和极性形成

• 发表时间: 2007
• 期刊: Nou 21 10
• 作者: Inagaki;N.;Toriyama;M.;Shimada;T
• 通讯作者: T

Shootinl:a protein involved in organization of an asymmetric signal for neuronal polarization

Shootinl：一种参与神经元极化不对称信号组织的蛋白质

• 发表时间: 2006
• 期刊: J. Cell Biol. 175
• 作者: Toriyama M. Shimada T.;Kim K.B.;Mitsuba M.;Nomura E.;Katsuta K.;Sakumura Y.;Roepstorff P.;Inagaki N.,
• 通讯作者: Inagaki N.,

Neuronal Process Outgrowth., In Lajtha F.W. (ed): Handbook of Neurochemistry and Molecular Neurobiology

神经元过程的生长，Lajtha F.W.（编辑）：神经化学和分子神经生物学手册

• 作者: Mori T.;Inagaki N.;Kamiguchi H.
• 通讯作者: Kamiguchi H.