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

Shootin1 interacts with actin retrograde flow and L1-CAM to promote axon outgrowth.
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DOI:
10.1083/jcb.200712138
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发表时间:
2008-06-02
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Inagaki N
Inagaki N
中科院分区:
其他
文献类型:
--
作者:
Shimada T;Toriyama M;Uemura K;Kamiguchi H;Sugiura T;Watanabe N;Inagaki N

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肌动蛋白在神经生长锥边缘附近聚合,肌动蛋白丝在丝状足和板足呈逆行运动。生长锥内肌动蛋白丝逆行流动与细胞粘附分子(cam)之间的联系被认为是轴突生长和引导的机制之一。然而,这种联系的分子基础仍然难以捉摸。本研究表明,在培养的大鼠海马神经元轴突生长锥中,shootin1与肌动蛋白丝逆行流和L1-CAM相互作用,从而介导它们之间的联系。通过干扰shootin1 RNA或干扰shootin1与肌动蛋白丝流之间的相互作用来削弱这种联系,会抑制l1依赖性轴突的生长,而通过过度表达shootin1来增强这种联系,则会促进神经突的生长。这些结果加强了轴突生长的肌动蛋白流动- cam联动模型(“离合器”模型),并表明shootin1是参与这一机制的关键分子。
Actin polymerizes near the leading edge of nerve growth cones, and actin filaments show retrograde movement in filopodia and lamellipodia. Linkage between actin filament retrograde flow and cell adhesion molecules (CAMs) in growth cones is thought to be one of the mechanisms for axon outgrowth and guidance. However, the molecular basis for this linkage remains elusive. Here, we show that shootin1 interacts with both actin filament retrograde flow and L1-CAM in axonal growth cones of cultured rat hippocampal neurons, thereby mediating the linkage between them. Impairing this linkage, either by shootin1 RNA interference or disturbing the interaction between shootin1 and actin filament flow, inhibited L1-dependent axon outgrowth, whereas enhancing the linkage by shootin1 overexpression promoted neurite outgrowth. These results strengthen the actin flow–CAM linkage model (“clutch” model) for axon outgrowth and suggest that shootin1 is a key molecule involved in this mechanism.
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