title: LIS1 and NDEL1 coordinate the plus-end-directed transport of cytoplasmic dynein.
abstract: LIS1 was first identified as a gene mutated in human classical lissencephaly sequence. LIS1 is required for dynein activity, but the underlying mechanism is poorly understood. Here, we demonstrate that LIS1 suppresses the motility of cytoplasmic dynein on microtubules (MTs), whereas NDEL1 releases the blocking effect of LIS1 on cytoplasmic dynein. We demonstrate that LIS1, cytoplasmic dynein and MT fragments co-migrate anterogradely. When LIS1 function was suppressed by a blocking antibody, anterograde movement of cytoplasmic dynein was severely impaired. Immunoprecipitation assay indicated that cytoplasmic dynein forms a complex with LIS1, tubulins and kinesin-1. In contrast, immunoabsorption of LIS1 resulted in disappearance of co-precipitated tubulins and kinesin. Thus, we propose a novel model of the regulation of cytoplasmic dynein by LIS1, in which LIS1 mediates anterograde transport of cytoplasmic dynein to the plus end of cytoskeletal MTs as a dynein-LIS1 complex on transportable MTs, which is a possibility supported by our data.
authors.affiliation: Department of Genetic Disease Research, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Yamada
authors.forename: Shiori
authors.initials: S
authors.lastname: Toba
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Koji
authors.initials: K
authors.lastname: Haratani
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mori
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yano
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mimori-Kiyosue
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kyoko
authors.initials: K
authors.lastname: Itoh
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiki
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
authors.forename: Anthony
authors.initials: A
authors.lastname: Wynshaw-Boris
authors.forename: Takayuki
authors.initials: T
authors.lastname: Torisawa
authors.forename: Yoko Y
authors.initials: YY
authors.lastname: Toyoshima
authors.forename: Shinji
authors.initials: S
authors.lastname: Hirotsune
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism*; D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D036681:Fluorescence Recovery After Photobleaching; D006801:Humans; D016547:Kinesins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008869:Microtubule-Associated Proteins; C421108:NDEL1 protein, human; D011993:Recombinant Fusion Proteins; C498585:TUBB3 protein, human; D014404:Tubulin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; D004398:Dyneins; D016547:Kinesins
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