mNUDC is required for plus‐end‐directed transport of cytoplasmic dynein and dynactins by kinesin‐1
mNUDC is required for plus‐end‐directed transport of cytoplasmic dynein and dynactins by kinesin‐1
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DOI：
10.1038/emboj.2009.378
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发表时间：
2010-02
期刊：
影响因子：
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通讯作者：
Masami Yamada;S. Toba;Takako Takitoh;Yuko Yoshida;D. Mori;Takeshi Nakamura;A. Iwane;T. Yanagida-T.-Yanag
中科院分区：
文献类型：
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作者：
Masami Yamada;S. Toba;Takako Takitoh;Yuko Yoshida;D. Mori;Takeshi Nakamura;A. Iwane;T. Yanagida-T.-Yanag
缺脑畸形是一种由神经元迁移缺陷引起的毁灭性神经系统疾病。is1（或pafah1b1）基因被确定为无脑畸形患者的突变基因，并被发现调节细胞质动力蛋白的功能和定位。特别是，LIS1作为细胞质动力蛋白- LIS1微管复合物的一部分，以依赖于动力蛋白- 1的方式对细胞质动力蛋白的顺行运输至关重要。然而，胞质动力蛋白- lis1微管复合物结合动力蛋白- 1的潜在机制尚不清楚。在这里，我们报道了mNUDC（哺乳动物NUDC）与kinesin‐1相互作用，并且是kinesin‐1顺行运输细胞质动力蛋白复合物所必需的。mNUDC在含dynactin复合物的顺行运输中也是必需的。mNUDC的抑制严重抑制了不同细胞质动力蛋白和动力蛋白复合物的顺行运输，而动力蛋白- 1的运动性保持不变。重建实验清楚地表明，mNUDC介导动力蛋白或动力蛋白复合物与kinesin‐1的相互作用，并支持它们通过kinesin‐1运输。我们的研究结果揭示了mNUDC在动力蛋白- 1顺行运输动力蛋白和动力蛋白中的重要作用。
Lissencephaly is a devastating neurological disorder caused by defective neuronal migration. TheLIS1(orPAFAH1B1) gene was identified as the gene mutated in lissencephaly patients, and was found to regulate cytoplasmic dynein function and localization. In particular, LIS1 is essential for anterograde transport of cytoplasmic dynein as a part of the cytoplasmic dynein–LIS1–microtubule complex in a kinesin‐1‐dependent manner. However, the underlying mechanism by which a cytoplasmic dynein–LIS1–microtubule complex binds kinesin‐1 is unknown. Here, we report that mNUDC (mammalian NUDC) interacts with kinesin‐1 and is required for the anterograde transport of a cytoplasmic dynein complex by kinesin‐1. mNUDC is also required for anterograde transport of a dynactin‐containing complex. Inhibition of mNUDC severely suppressed anterograde transport of distinct cytoplasmic dynein and dynactin complexes, whereas motility of kinesin‐1 remained intact. Reconstruction experiments clearly demonstrated that mNUDC mediates the interaction of the dynein or dynactin complex with kinesin‐1 and supports their transport by kinesin‐1. Our findings have uncovered an essential role of mNUDC for anterograde transport of dynein and dynactin by kinesin‐1.