Slow axonal transport driven by directional actin turnover

由定向肌动蛋白周转驱动的缓慢轴突运输

• 批准号: 23370088
• 负责人: INAGAKI Naoyuki
• 金额: $ 12.81万
• 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: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23370088/
• 关键词: 脳・神経; 発生・分化; 神経科学; 軸索輸送; 細胞骨格; 分子クラッチ; Shootin1; アクチン線維

Although actin and associated proteins are essential for axonal extension, how they are transported along axons remains unclear. Here we show that actin filaments (F-actins) and associated proteins migrate toward the axonal growth cone by means of directional actin polymerization/depolymerization, called treadmilling. F-actins migrating along axonal shafts underwent treadmilling, with their polymerizing ends oriented toward the growth cone. F-actins were anchored to the plasma membrane through the cell adhesion molecule L1-CAM and the linker protein shootin1. Migration of F-actins depended on their polymerization and substrate anchorage, and directional counter-forces associated with F-actin migration were detected on the substrate. Actin-associated proteins co-migrated with F-actins by interacting with the filaments. Our findings reveal a new mode of intracellular transport, which supplies actin and associated proteins to the axonal leading edge, thereby promoting its protrusion.

虽然肌动蛋白和相关蛋白质是轴突延伸所必需的，但它们如何沿沿着运输仍不清楚。在这里，我们表明，肌动蛋白丝（F-肌动蛋白）和相关的蛋白质迁移到轴突生长锥的定向肌动蛋白聚合/解聚，称为螺旋铣削。F-肌动蛋白迁移沿着轴突轴进行螺旋铣削，其聚合端朝向生长锥。F-肌动蛋白通过细胞粘附分子L1-CAM和连接蛋白shootin 1锚定在质膜上。F-肌动蛋白的迁移依赖于它们的聚合和基板锚定，和定向反作用力与F-肌动蛋白迁移检测基板上。肌动蛋白相关蛋白与F-肌动蛋白共同迁移的相互作用的细丝。我们的研究结果揭示了一种新的细胞内运输模式，它提供肌动蛋白和相关蛋白的轴突前缘，从而促进其突起。

项目成果

Ceramic Coating of Liposomal Gene Carrier for Minimizing Toxicity to Primary Hippocampal Neurons

• DOI: 10.1246/cl.130541
• 发表时间: 2013-07
• 期刊: Chemistry Letters
• 影响因子: 1.6
• 作者: Keishiro Tahara;Takanobu Moriuchi;Miku Tsukui;A. Hirota;T. Maeno;Michinori Toriyama;N. Inagaki;J. Kikuchi

Cortactin functions as a clutch molecule to promote axon outgrowth

Cortactin 作为离合器分子促进轴突生长

• 发表时间: 2013
• 作者: 久保祐亮;鳥山道則;小沢哲;池田和司;杉浦忠男;稲垣直之
• 通讯作者: 稲垣直之

Mechanisms for the axon-specific accumulation of an axonal protein JIP1

轴突蛋白 JIP1 的轴突特异性积累机制

• 发表时间: 2011
• 作者: Takanori Maeno;Michinori Toriyama;Naoyuki Inagaki
• 通讯作者: Naoyuki Inagaki

脳発生におけるShootin1およびShootin2の機能解析

Shootin1和Shootin2在大脑发育中的功能分析

• 发表时间: 2013
• 作者: Iwatani H;Iio K;Nagasawa Y;Yamamoto R;Horii A;Okuzaki D;Inohara H;Nojima H;Imai E;Rakugi H;Isaka Y.;吉田亙，島田忠之，鳥山道則，河野憲二，稲垣直之
• 通讯作者: 吉田亙，島田忠之，鳥山道則，河野憲二，稲垣直之

Slow axonal transport driven by directional actin treadmilling

定向肌动蛋白跑步机驱动的慢速轴突运输

• 发表时间: 2012
• 作者: 勝野弘子;鳥山道則;作村諭一;池田和司;水野健作;稲垣直之
• 通讯作者: 稲垣直之