Cai Qian, Gerwin Claudia, Sheng Zu-Hang
Synaptic Function Unit, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
J Cell Biol. 2005 Sep 12;170(6):959-69. doi: 10.1083/jcb.200506042.
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.
在神经元中，线粒体在轴突和突触处的正确分布对于神经传递、突触可塑性和轴突生长至关重要。然而，线粒体在整个长神经元突起中运输的潜在机制仍不清楚。在此，我们报告Syntaxin结合蛋白在神经元线粒体运输中起关键作用。Syntaxin结合蛋白是一种外周膜相关蛋白，通过其羧基末端尾巴靶向线粒体。利用活培养神经元中的实时成像，我们证明相当一部分Syntaxin结合蛋白与线粒体沿神经元突起共定位并共同迁移。用靶向小干扰RNA敲低Syntaxin结合蛋白表达或干扰Syntaxin结合蛋白与驱动蛋白-1重链的相互作用，会通过损害线粒体的顺向移动来降低轴突突起内的线粒体密度。这些发现共同表明，Syntaxin结合蛋白作为一种连接分子，能够将线粒体细胞器附着到基于微管的驱动蛋白-1上，进而促进线粒体向神经元突起的顺向运输。
