mNUDC is required for plus‐end‐directed transport of cytoplasmic dynein and dynactins by kinesin‐1 |
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| Authors: | Masami Yamada Shiori Toba Takako Takitoh Yuko Yoshida Daisuke Mori Takeshi Nakamura Atsuko H Iwane Toshio Yanagida Hiroshi Imai Li‐yuan Yu‐Lee Trina Schroer Anthony Wynshaw‐Boris Shinji Hirotsune |
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| Institution: | 1. Department of Genetic Disease Research, Graduate School of Medicine, Osaka City University, Osaka, Japan;2. Laboratory of Bioimaging and Cell Signaling, Graduate School of Biostudies, Kyoto University Yoshida Konoe‐cho, Kyoto, Japan;3. Laboratories for Nanobiology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan;4. ERATO Actin Filament Dynamics Project, Japan Science and Technology Agency, RIKEN SPring‐8 Center, Sayo, Hyogo, Japan;5. Program in Cell and Molecular Biology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA;6. Department of Biology, The Johns Hopkins University, Baltimore, MD, USA;7. Department of Pediatrics and Institute for Human Genetics University of California, San Francisco School of Medicine, Parnassus, San Francisco, CA, USA |
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| Abstract: | Lissencephaly is a devastating neurological disorder caused by defective neuronal migration. The LIS1 (or PAFAH1B1) 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. |
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| Keywords: | adaptor dynein kinesin‐1 Lis1 mNUDC |
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