Elucidation of regulatory mechanisms of cytoplasmic dynein.

• Project/Area Number: 20390084
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Osaka City University
• Principal Investigator: HIROTSUNE Shinji Osaka City University, 大学院・医学研究科, 教授 (80337526)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2008: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
• Keywords: (B)細胞医化学 / 中枢神経系 / モータータンパク質 / 染色体分離 / 細胞分裂 / LIS1 / 染色体分配 / 細胞質ダイニン / 紡錘体形成 / 発がん / 細胞骨格 / 軸索伸展 / 神経細胞 / 脳機能

Research 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. 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. Our findings have uncovered an essential role of mNUDC for anterograde transport of dynein and dynactin by kinesin-1

Research Products

• [Journal Article] Functional dissection of LIS1 and NDEL1 towards understanding the molecular mechanisms of cytoplasmic dynein regulation (2011)
  • Author(s): Torisawa, T., Nakayama, A., Furuta, K., Yamada, M., Hirotsune, S., Toyoshima, Y. Y.
  • Journal Title: J Biol Chem 286 Pages: 1959-1965
  • Peer Reviewed
• [Journal Article] Global developmental gene expression and pathway analysis of normal brain development and mouse models of human neuronal migration defects (2011)
  • Author(s): Pramparo, T., Libiger, O., Jain, S., Li, H., Youn, Y. H., Hirotsune, S., Schork, N. J., Wynshaw-Boris, A.
  • Journal Title: PLoS Genet 7
  • Peer Reviewed
• [Journal Article] Trichoplein controls microtubule anchoring at the centrosome by binding to Odf2 and ninein (2011)
  • Author(s): Ibi, M., Zou, P., Inoko, A., Shiromizu, T., Matsuyama, M., Hayashi, Y., Enomoto, M., Mori, D., Hirotsune, S., Kiyono, T., Tsukita, S., Goto, H., Inagaki, M.
  • Journal Title: J Cell Sci
  • Peer Reviewed
• [Journal Article] Global developmental gene expression and pathway analysis of normal brain development and mouse models of human neuronal migration defects. (2011)
  • Author(s): Pramparo T, Libiger O, Jain S, Li H, Youn YH, Hirotsune S, Schork NJ, Wynshaw-Boris A.
  • Journal Title: PLoS Genet. Volume: 3
  • Peer Reviewed
• [Journal Article] Trichoplein controls microtubule anchoring at the centrosome by binding to Odf2 and ninein. (2011)
  • Author(s): Ibi M, Zou P, Inoko A, Shiromizu T, Matsuyama M, Hayashi Y, Enomoto M, Mori D, Hirotsune S, Kiyono T, Tsukita S, Goto H, Inagaki M.
  • Journal Title: J Cell Sci. Volume: 124 Pages: 857-964
  • Peer Reviewed
• [Journal Article] Functional dissection of LIS1 and NDEL1 towards understanding the molecular mechanisms of cytoplasmic dynein regulation. (2011)
  • Author(s): Torisawa T, Nakayama A, Furuta K, Yamada M, Hirotsune S, Toyoshima YY.
  • Journal Title: J Biol Chem. Volume: 286 Pages: 1954-1965
  • Peer Reviewed
• [Journal Article] mNUDC is required for plus-end-directed transport of cytoplasmic dynein and dynactins by kinesin-1 (2010)
  • Author(s): Yamada, M., Toba, S., Takitoh, T., Yoshida, Y., Mori, D., Nakamura, T., Iwane, A. H., Yanagida, T., Imai, H., Yu-Lee, L. Y., Schroer, T., Wynshaw-Boris, A., Hirotsune, S.
  • Journal Title: EMBO J 29 Pages: 517-531
  • Peer Reviewed
• [Journal Article] Novel embryonic neuronal migration and proliferation defects in Dcx mutant mice are exacerbated by Lis1 reduction (2010)
  • Author(s): Pramparo, T., Youn, Y. H., Yingling, J., Hirotsune, S., Wynshaw-Boris, A.
  • Journal Title: J Neurosci 30 Pages: 3002-3012
  • Peer Reviewed
• [Journal Article] mNUDC is required for plus-end directed transport of cytoplasmic dynein and dynactins by kinesin-1. (2010)
  • Author(s): Yamada M, Yoshida Y, Mori D, Takitoh T, Nakamura T, H.Iwane A, Yanagida T, Yu-Lee L, Wynshaw-Boris A, Hirotsune S.
  • Journal Title: EMBO J 29 Pages: 517-531
  • Peer Reviewed
• [Journal Article] Distinct dose-dependent cortical neuronal migration and neurite extension defects in Lis1 and Ndel1 mutant mice (2009)
  • Author(s): Youn, Y. H., Pramparo, T., Hirotsune, S., Wynshaw-Boris, A.
  • Journal Title: J Neurosci 29 Pages: 15520-15530
  • Peer Reviewed
• [Journal Article] Inhibition of calpain increases LIS1 expression and partially rescues in vivo phenotypes in a mouse model of lissencephaly (2009)
  • Author(s): Yamada, M., Yoshida, Y., Mori, D., Takitoh, T., Kengaku, M., Umeshima, H., Takao, K., Miyakawa, T., Sato, M., Sorimachi, H., Wynshaw-Boris, A., Hirotsune, S.
  • Journal Title: Nat Med 15 Pages: 1202-1207
  • Peer Reviewed
• [Journal Article] An essential role of the aPKC-Aurora A-NDEL1 pathway in neurite elongation by modulation of microtubule dynamics (2009)
  • Author(s): Mori, D., Yamada, M., Mimori-Kiyosue, Y., Shirai, Y., Suzuki, A., Ohno, S., Saya, H., Wynshaw-Boris, A., Hirotsune, S.
  • Journal Title: Nat Cell Biol 11 Pages: 1057-1068
  • Peer Reviewed
• [Journal Article] CRMP-2 directly binds to cytoplasmic dynein and interferes with its activity (2009)
  • Author(s): Arimura, N., Hattori, A., Kimura, T., Nakamuta, S., Funahashi, Y., Hirotsune, S., Furuta, K., Urano, T., Toyoshima, Y. Y., Kaibuchi, K.
  • Journal Title: J Neurochem 111 Pages: 380-390
  • Peer Reviewed
• [Journal Article] An Essential Role of the aRKC-Aurora A-NDEL1 Pathway on Neurite Elongation via Modulation of Microtubule Dynamics. (2009)
  • Author(s): Daisuke Mori, Masami Yamada, Yuko Mimori-Kiyosue, Yasuhito Shirai, Atsushi Suzuki, Shigeo Ohno, Hideaki Saya, Anthony Wynshaw-Boris, Hirotsune S.
  • Journal Title: Nature Cell Biology 11 Pages: 1057-1068
  • Peer Reviewed
• [Journal Article] nhibition of calpain increases LIS1 and partially rescues in vivo phenotypes in Lis1 mutant mice : a potential therapy for lissencephaly. (2009)
  • Author(s): Yamada M, Yoshida Y, Mori D, Rakitoh T, Kengaku M, Satoh M, Sorimachi H, Takao K, Miyakawa T, Wynshaw-Boris A, Hirotsune S.
  • Journal Title: Nature Medicine 15 Pages: 1202-1207
  • Peer Reviewed
• [Journal Article] Neuroepithelial stem cell proliferation requires LIS1 for precise spindle orientation and symmetric division (2008)
  • Author(s): Yingling, J., Youn, Y. H., Darling, D., Toyo-Oka, K., Pramparo, T., Hirotsune, S., Wynshaw-Boris, A.
  • Journal Title: Cell 132 Pages: 474-486
  • Peer Reviewed
• [Journal Article] LIS1 and NDEL1 coordinate the plus-end-directed transport of cytoplasmic dynein (2008)
  • Author(s): Yamada, M., Toba, S., Yoshida, Y., Haratani, K., Mori, D., Yano, Y., Mimori-Kiyosue, Y., Nakamura, T., Itoh, K., Fushiki, S., Setou, M., Wynshaw-Boris, A., Torisawa, T., Toyoshima, Y. Y., Hirotsune, S.
  • Journal Title: EMBO J 27 Pages: 2471-2483
  • Peer Reviewed
• [Remarks] ホームページ等
  • URL: http://www.med.osaka-cu.ac.jp/biochem2/index.html