Syntabulin-mediated anterograde transport of mitochondria along neuronal processes.
Syntabulin-mediated anterograde transport of mitochondria along neuronal processes.
复制标题
征素介导的线粒体沿神经元过程的顺行转运。
DOI：
10.1083/jcb.200506042
复制
发表时间：
2005-09-12
影响因子：
7.8
通讯作者：
Sheng, Zu-Hang
中科院分区：
文献类型：
--
作者：
Cai, Qian;Gerwin, Claudia;Sheng, Zu-Hang
在神经元中，线粒体在轴突和突触中的适当分布对于神经传递、突触可塑性和轴突生长至关重要。然而，线粒体运输整个长的神经元过程的机制仍然难以捉摸。在这里，我们报告，syntabulin在神经元线粒体贩运中起着关键作用。合成表蛋白是一种外周膜相关蛋白，通过其羧基末端尾靶向线粒体。使用实时成像在活的培养神经元，我们证明了一个显着的部分syntabulin共定位和共迁移与线粒体沿着神经元的过程。用靶向小干扰RNA敲低合成表蛋白表达或干扰合成表蛋白-驱动蛋白-1重链相互作用通过损害线粒体的顺行运动来降低轴突过程内的线粒体密度。这些研究结果共同表明，syntabulin作为一个连接分子，能够连接线粒体细胞器的微管为基础的运动驱动蛋白-1，并反过来，有助于顺行运输线粒体的神经元过程。
In neurons, proper distribution of mitochondria in axons and at synapses is critical for neurotransmission, synaptic plasticity, and axonal outgrowth. However, mechanisms underlying mitochondrial trafficking throughout the long neuronal processes have remained elusive. Here, we report that syntabulin plays a critical role in mitochondrial trafficking in neurons. Syntabulin is a peripheral membrane-associated protein that targets to mitochondria through its carboxyl-terminal tail. Using real-time imaging in living cultured neurons, we demonstrate that a significant fraction of syntabulin colocalizes and co-migrates with mitochondria along neuronal processes. Knockdown of syntabulin expression with targeted small interfering RNA or interference with the syntabulin–kinesin-1 heavy chain interaction reduces mitochondrial density within axonal processes by impairing anterograde movement of mitochondria. These findings collectively suggest that syntabulin acts as a linker molecule that is capable of attaching mitochondrial organelles to the microtubule-based motor kinesin-1, and in turn, contributes to anterograde trafficking of mitochondria to neuronal processes.