Spatiotemporal control of cell functions by Rho GTPases ; mechanisms and physiological roles

2010 Fiscal Year Final Research Report

• Project/Area Number: 18002015
• Research Category: Grant-in-Aid for Specially Promoted Research
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: NARUMIYA Shuh Kyoto University, 医学研究科, 教授 (70144350)
• Project Period (FY): 2006 – 2010
• Keywords: Rho / アクチン / 微小管 / 細胞周期 / 細胞質分裂

Research Abstract

The small GTPase Rho functions as a molecular switch of cell morphogenesis, adhesion, migration and division by acting on downstream signaling molecules. Here we studied the spatiotemoral role of this signaling in cultured cells and the body. We revealed the role and mechanism of the Rho signaling in cell migration and cell division in cultured cells and further found that this pathway plays an essential role in development such as embryo vasculogenesis and proper path finding of axon, and that this pathway is exploited by oncogenes in cell transformation and tumorigenesis.

Research Products

• [Journal Article] Rotational movement of the formin mDia1 along the double helical strand of an actin filament. (2011)
  • Author(s): Mizuno H, Higashida C, Yuan Y, Ishizaki T, Narumiya S, Watanabe N.
  • Journal Title: Science. 331 Pages: 80-83
  • Peer Reviewed
• [Journal Article] Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells. (2010)
  • Author(s): Tanizaki H, Egawa G, Inaba K, Honda T, Nakajima S, Moniaga CS, Otsuka A, Ishizaki T, Tomura M, Watanabe T, Miyachi Y, Narumiya S, Okada T, Kabashima K.
  • Journal Title: Blood. 116 Pages: 5875-5884
  • Peer Reviewed
• [Journal Article] Dual roles of PGE2-EP4 signaling in mouse experimental autoimmune encephalomyelitis. (2010)
  • Author(s): Esaki Y, Li Y, Sakata D, Yao C, Segi-Nishida E, Matsuoka T, Fukuda K, Narumiya S.
  • Journal Title: Proc Natl Acad Sci USA. 107 Pages: 12233-12238
  • Peer Reviewed
• [Journal Article] Molecular pathway and cell state responsible for dissociation-induced apoptosis in human pluripotent stem cells. (2010)
  • Author(s): Ohgushi M, Matsumura M, Eiraku M, Murakami K, Aramaki T, Nishiyama A, Muguruma K, Nakano T, Suga H, Ueno M, Ishizaki T, Suemori H, Narumiya S, Niwa H, Sasai Y.
  • Journal Title: Cell Stem Cell. 7 Pages: 225-239
  • Peer Reviewed
• [Journal Article] mDia1 targets v-Src to the cell periphery and facilitates cell transformation, tumorigenesis, and invasion. (2010)
  • Author(s): Tanji M, Ishizaki T, Ebrahimi S, Tsuboguchi Y, Sukezane T, Akagi T, Frame MC, Hashimoto N, Miyamoto S, Narumiya S.
  • Journal Title: Mol Cell Biol. 19 Pages: 4604-4615
  • Peer Reviewed
• [Journal Article] Rho and anillin-dependent control of mDia2localization and function in cytokinesis. (2010)
  • Author(s): Watanabe S, Okawa K, Miki T, Sakamoto S, Morinaga T, Segawa K, Arakawa T, Kinoshita M, Ishizaki T, Narumiya S.
  • Journal Title: Mol Biol Cell. 21 Pages: 3193-3204
  • Peer Reviewed
• [Journal Article] Central control of fever and female body temperature by RANKL/RANK. (2009)
  • Author(s): Hanada R, Leibbrandt A, Hanada T, Kitaoka S, Furuyashiki T, Fujihara H, Trichereau J, Paolino M, Qadri F, Plehm R, Klaere S, Komnenovic V, Mimata H, Yoshimatsu H, Takahashi N, von Haeseler A, Bader M, Kilic SS, Ueta Y, Pifl C, Narumiya S,Penninger JM.
  • Journal Title: Nature. 462 Pages: 505-509
  • Peer Reviewed
• [Journal Article] Prostaglandin F(2a) receptor signaling facilitates bleomycin-induced pulmonary fibrosis independently of transforming growth factor-beta. (2009)
  • Author(s): Oga T, Matsuoka T, Yao C, Nonomura K, Kitaoka S, Sakata D, Kita Y, Tanizawa K, Taguchi Y, Chin K, Mishima M, Shimizu T, Narumiya S.
  • Journal Title: Nat Med. 15 Pages: 1426-1430
  • Peer Reviewed
• [Journal Article] Imatinib mesylate (STI571)-induced cell edge translocation of kinase-active and kinase-defective Abelson kinase: requirements of myristoylation and src homology 3 domain. (2009)
  • Author(s): Fujita A, Shishido T, Yuan Y, Inamoto E, Narumiya S, Watanabe N.
  • Journal Title: Mol Pharmacol. 75 Pages: 75-84
  • Peer Reviewed
• [Journal Article] Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion. (2009)
  • Author(s): Yao C, Sakata D, Esaki Y, Li Y, Matsuoka T, Kuroiwa K, Sugimoto Y, Narumiya S.
  • Journal Title: Nat Med. 15 Pages: 633-640
  • Peer Reviewed
• [Journal Article] RhoA/Rho kinase signaling in the cumulus mediates extracellular matrix assembly. (2009)
  • Author(s): Yodoi R, Tamba S, Morimoto K, Segi-Nishida E, Nishihara M, Ichikawa A, Narumiya S, Sugimoto Y.
  • Journal Title: Endocrinology. 150 Pages: 3345-3352
  • Peer Reviewed
• [Journal Article] Cdc42 and Rac family GTPases regulate mode and speed but not direction of primary fibroblast migration during platelet-derived growth factor-dependent chemotaxis. (2009)
  • Author(s): Monypenny J, Zicha D, Higashida C, Oceguera-Yanez F, Narumiya S, Watanabe N.
  • Journal Title: Mol Cell Biol. 29 Pages: 2730-2747
  • Peer Reviewed
• [Journal Article] mDia2shuttles between the nucleus and the cytoplasm through the importin-{a}/{b}- and CRM1-mediated nuclear transport mechanism. (2009)
  • Author(s): Miki T, Okawa K, Sekimoto T, Yoneda Y, Watanabe S, Ishizaki T, Narumiya S.
  • Journal Title: J Biol Chem. 284 Pages: 5753-5762
  • Peer Reviewed
• [Journal Article] The mammalian formin FHOD1 is activated through phosphorylation by ROCK and mediates thrombin-induced stress fibre formation in endothelial cells. (2008)
  • Author(s): Takeya R, Taniguchi K, Narumiya S, Sumimoto H.
  • Journal Title: EMBO J. 27 Pages: 618-628
  • Peer Reviewed
• [Journal Article] G-actin regulates rapid induction of actin nucleation by mDia1 to restore cellular actin polymers. (2008)
  • Author(s): Higashida C, Suetsugu S, Tsuji T, Monypenny J, Narumiya S, Watanabe N.
  • Journal Title: J Cell Sci. 121 Pages: 3403-3412
  • Peer Reviewed
• [Journal Article] mDia2 induces the actin scaffold for the contractile ring and stabilizes its position during cytokinesis in NIH 3T3 cells. (2008)
  • Author(s): Watanabe S, Ando Y, Yasuda S, Hosoya H, Watanabe N, Ishizaki T, Narumiya S.
  • Journal Title: Mol Biol Cell. 19 Pages: 2328-2338
  • Peer Reviewed
• [Journal Article] Facilitation of Th1-mediated immune response by prostaglandin E receptor EP1. (2007)
  • Author(s): Nagamachi M, Sakata D, Kabashima K, Furuyashiki T, Murata T, Segi-Nishida E, Soontrapa K, Matsuoka T, Miyachi Y, Narumiya S.
  • Journal Title: J Exp Med. 204 Pages: 2865-2874
  • Peer Reviewed
• [Journal Article] Impaired T lymphocyte trafficking in mice deficient in an actin-nucleating protein, mDia1. (2007)
  • Author(s): Sakata D, Taniguchi H, Yasuda S, Adachi-Morishima A, Hamazaki Y, Nakayama R, Miki T, Minato N, Narumiya S.
  • Journal Title: J Exp Med. 204 Pages: 2031-2038
  • Peer Reviewed
• [Journal Article] Inactivation of Rho GTPases with Clostridium difficile toxin B impairs centrosomal activation of Aurora-A in G2/M transition of HeLa cells. (2007)
  • Author(s): Ando Y, Yasuda S, Oceguera-Yanez F, Narumiya S.
  • Journal Title: Mol Biol Cell. 18 Pages: 3752-3763
  • Peer Reviewed
• [Journal Article] Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis. (2006)
  • Author(s): Honda T, Segi-Nishida E, Miyachi Y, Narumiya S.
  • Journal Title: J Exp Med. 203 Pages: 325-335
  • Peer Reviewed
• [Journal Article] The Rho-mDia1 pathway regulates cell polarity and focal adhesion turnover in migrating cells through mobilizing Apc and c-Src. (2006)
  • Author(s): Yamana N, Arakawa Y, Nishino T, Kurokawa K, Tanji M, Itoh RE, Monypenny J, Ishizaki T, Bito H, Nozaki K, Hashimoto N, Matsuda M, Narumiya S.
  • Journal Title: Mol Cell Biol. 26 Pages: 6844-6858
  • Peer Reviewed
• [Presentation] Phenotype Analysis of Mice Deficient in Actin Nucleator, mDia (2010)
  • Author(s): Narumiya S.
  • Organizer: 4th Mechanobiology Workshop and Biophysical Society Meeting
  • Place of Presentation: Singapore
  • Year and Date: 20101109-20101112
• [Presentation] Functions of the Rho-mDia pathway in the body; lessons from knockout mice (2009)
  • Author(s): Narumiya S.
  • Organizer: The Gordon Research Conference on "Mechanisms of Cell Signaling"
  • Place of Presentation: Magdalene College, Oxoford, U.K.
  • Year and Date: 20090823-20090828
• [Presentation] Rho-mDia pathway, Src and cell transformation (2008)
  • Author(s): Narumiya S.
  • Organizer: Gordon Conference on Phosphorylation and G-protein mediated Signaling Networks
  • Place of Presentation: University of New England, Maine, U.S.A.
  • Year and Date: 20080615-20080620
• [Presentation] The Rho-mDia Pathway in Cell Transformaiton and Migration (2008)
  • Author(s): Narumiya S.
  • Organizer: The AACR Special Conference in Cancer Researh on Cytoskeleotn Signaling in Cancer
  • Place of Presentation: San Diego, U.S.A.
  • Year and Date: 20080203-20080205
• [Presentation] mDia Isoforms Mediate Delivery of c-Src and Spindle Orientation through Actin Cytoskeleton; A Conserved Mechanism from Yeast to Mammals (2007)
  • Author(s): Narumiya S.
  • Organizer: ASCB-ECF Summer Meeting Dynamic Interplay Between Cytoskeletal and Membrane Systems, Dijon Congrexpo
  • Place of Presentation: Dijon, France.
  • Year and Date: 20070627-20070630
• [Presentation] Rho signaling : Roles and Mechanism in Cell Morphogenesis and Movement (2007)
  • Author(s): Narumiya S.
  • Organizer: Dana-Farber Cancer Institute Seminars in Oncology
  • Place of Presentation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, U.S.A.
  • Year and Date: 2007-04-03
• [Presentation] Rho GTPases in animal cell mitosis (2006)
  • Author(s): Narumiya S.
  • Organizer: FASEB Summer Research Conference on Regulation & Function of Small GTPases
  • Place of Presentation: Vermont Academy, Vermont, U.S.A.
  • Year and Date: 20060715-20060720
• [Presentation] Cytoskeleton Remodeling by Rho GTPases and Effectors in cell morphogenesis, migration and mitosis.The Symposium on Cytoskeleon: dynamics and structural basis of cytoskeleton assembly (2006)
  • Author(s): Narumiya S.
  • Organizer: The 20th IUBMB International Congress of Biochemistry and Molecular Biology and the 11th FAOBMB Congress
  • Place of Presentation: Kyoto, Japan.
  • Year and Date: 20060618-20060623
• [Remarks] ホームページ
  • URL: http://www5.mfour.med.kyoto-u.ac.jp/