title: mNUDC is required for plus-end-directed transport of cytoplasmic dynein and dynactins by kinesin-1.
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.
authors.affiliation: Department of Genetic Disease Research, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Yamada
authors.forename: Shiori
authors.initials: S
authors.lastname: Toba
authors.forename: Takako
authors.initials: T
authors.lastname: Takitoh
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Atsuko H
authors.initials: AH
authors.lastname: Iwane
authors.forename: Toshio
authors.initials: T
authors.lastname: Yanagida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imai
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Yu-Lee
authors.forename: Trina
authors.initials: T
authors.lastname: Schroer
authors.forename: Anthony
authors.initials: A
authors.lastname: Wynshaw-Boris
authors.forename: Shinji
authors.initials: S
authors.lastname: Hirotsune
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D056445:Cytoplasmic Dyneins / Q000378:metabolism*; D000072159:Dynactin Complex; D005727:Ganglia, Spinal / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D013552:Swine
chemical_list: D018797:Cell Cycle Proteins; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C512649:Nudc protein, mouse; D034741:RNA, Small Interfering; D056445:Cytoplasmic Dyneins; D016547:Kinesins