G protein-regulated trafficking analyzed by bio-imaging

• Project/Area Number: 17079009
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: MOCHIZUKI Naoki National Cardiovascular Center Research Institute, 循環器形態部, 部長 (30311426)
• Co-Investigator(Kenkyū-buntansha): FUKUHARA Shigetomo 国立循環器病センター研究所, 循環器形態部, 室長 (70332880) ; MASUDA Michitaka 国立循環器病センター研究所, 循環器形態部, 室長 (00190364) ; FUJITA Hisakazu 国立循環器病センター研究所, 循環器形態部, 室長 (30212187) ; KAWAHARA Atsuo 国立循環器病センター研究所, 循環器形態部, 室長 (10362518) ; MIURA Kouichi 国立循環器病センター研究所, 循環器形態部, 室員 (20360349)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥63,500,000 (Direct Cost: ¥63,500,000); Fiscal Year 2009: ¥13,600,000 (Direct Cost: ¥13,600,000); Fiscal Year 2008: ¥13,600,000 (Direct Cost: ¥13,600,000); Fiscal Year 2007: ¥13,600,000 (Direct Cost: ¥13,600,000); Fiscal Year 2006: ¥13,600,000 (Direct Cost: ¥13,600,000); Fiscal Year 2005: ¥9,100,000 (Direct Cost: ¥9,100,000)
• Keywords: 低分子量G蛋白 / 情報伝達 / 輸送 / VE-cadherin / Rap1 / ミオシン / 低分子量 / 低分子量蛋白

Research Abstract

低分子量GTP結合蛋白質(G蛋白質)は、細胞内情報伝達を制御する分子として不可欠である。細胞の形態や蛋白質・脂質の移動も制御している。分子の挙動・移動の分子メカニズムは、生きた細胞をイメージングすることによって理解できると考えた。低分子量G蛋白質Rap1による細胞間接着分子のvascular endothelial cadherin(VEC)分子の制御機構について、イメージングを駆使して研究し、Rap1がVECの安定化に重要であることを突き止めた。

Research Products

• [Journal Article] Vascular Endothelial-Cadherin Stabilizes at Cell-Cell Junctions by Anchoring to Circumferential Actin Bundles through α- and β-Catenins in Cyclic AMP-Epac-Rap1 Signal-activated Endothelial Cells. (2010)
  • Author(s): Noda K, Zhang J, Fukuhara S, Kunimoto S, Yoshimura M, Mochizuki N
  • Journal Title: Mol Biol Cell. 21 Pages: 584-96
• [Journal Article] Structural characteristics of BAR domain superfamily to sculpt the membrane. (2010)
  • Author(s): Masuda M, Mochizuki N
  • Journal Title: Semin Cell Dev Biol. 21 Pages: 391-398
• [Journal Article] Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and angiogenesis. (2010)
  • Author(s): Fukuhara S, Sako K, Noda K, Zhang J, Minami M, Mochizuki N
  • Journal Title: Histol Histopathol. 25 Pages: 387-96
• [Journal Article] Sphingosine 1-Phosphate Regulates Vascular Contraction via S1P3 Receptor: Investigation Based on a New S1P3 Receptor Antagonist. (2010)
  • Author(s): Murakami A, Takasugi H, Ohnuma S, Koide Y, Sakurai A, Takeda S, Hasegawa T, Sasamori J, Konno T, Hayashi K, Watanabe Y, Mori K, Sato Y, Takahashi A, Mochizuki N, Takakura N
  • Journal Title: Mol Pharmacol. 77 Pages: 704-713
• [Journal Article] Vascular Endothelial-Cadherin Stabilizes at Cell-Cell Junctions by Anchoring to Circumferential Actin Bundles through α- and β-Catenins in Cyclic AMP-Epac-Rapl Signal-activated Endothelial Cells. (2010)
  • Author(s): Noda K, Zhang J, Fukuhara S, Kunimoto S, Yoshimura M, Mochizuki N.
  • Journal Title: Mol.Biol.Cell 21 Pages: 584-596
  • Peer Reviewed
• [Journal Article] Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and angiogenesis. (2010)
  • Author(s): Fukuhara S, Sako K, Noda K, Zhang J, Minami M, Mochizuki N.
  • Journal Title: Histol.Histopathol. 25 Pages: 387-396
  • Peer Reviewed
• [Journal Article] Vascular integrity mediated by vascular endothelial cadherin and regulated by sphingosine 1-phosphate and angiopoietin-1. (2009)
  • Author(s): Mochizuki N
  • Journal Title: Circ. J. 73 Pages: 2183-2191
  • NAID: 10025937790
• [Journal Article] The sphingolipid transporter spns2 functions in migration of zebrafish myocardial precursors. (2009)
  • Author(s): Kawahara A, Nishi T, Hisano Y, Fukui H, Yamaguchi A, Mochizuki N
  • Journal Title: Science 323 Pages: 524-527
• [Journal Article] Angiopoietin-like protein 2 promotes chronic adipose tissue inflammation and obesity-related systemic insulin resistance. (2009)
  • Author(s): Tabata M, Kadomatsu T, Fukuhara S, Miyata K, Ito Y, Endo M, Urano T, Zhu HJ, Tsukano H, Tazume H, Kaikita K, Miyashita K, Iwawaki T, Shimabukuro M, Sakaguchi K, Ito T, Nakagata N, Yamada T, Katagiri H, Kasuga M, Ando Y, Ogawa H, Mochizuki N, Itoh H, Suda T, Oike Y.
  • Journal Title: Cell Metab 10 Pages: 178-188
• [Journal Article] Zyxin mediates actin fiber reorganization in epithelial-mesenchymal transition and contributes to endocardial morphogenesis. (2009)
  • Author(s): Mori M, Nakagami H, Koibuchi N, Miura K, Takami Y, Koriyama H, Hayashi H, Sabe H, Mochizuki N, Morishita R, Kaneda Y
  • Journal Title: Mol. Biol. Cell 20 Pages: 3115-3124
• [Journal Article] EphA2 Engages Git1 to Suppress Arf6 Activity Modulating Epithelial Cell-Cell Contacts. (2009)
  • Author(s): Miura K, Nam JM, Kojima C, Mochizuki N, Sabe H
  • Journal Title: Mol. Biol. Cell 20 Pages: 1949-1959
• [Journal Article] Angiopoietin-1 Induces Kruppel-like Factor 2 Expression through a Phosphoinositide 3-Kinase/AKT-dependent Activation of Myocyte Enhancer Factor 2. (2009)
  • Author(s): Sako K, Fukuhara S, Minami T, Hamakubo T, Song H, Kodama T, Fukamizu A, Gutkind JS, Koh GY, Mochizuki N
  • Journal Title: J. Biol. Chem. 284 Pages: 5592-5601
• [Journal Article] Differential function of Tie2 at cell-cell contacts and cell-substratum contacts regulated by angiopoietin-1. (2008)
  • Author(s): Fukuhara S, Sako K, Minami T, Noda K, Kim HK3, KodamT, Shibuya M, Takakura N, Koh GY, Mochizuki N
  • Journal Title: Nat. Cell Biol. 10 Pages: 513-526
• [Journal Article] Interaction of scaffolding adaptor protein Gab1 with tyrosine phosphatase SHP2 negatively regulates IGF-I-dependent myogenic differentiation via the ERK1/2 signaling pathway. (2008)
  • Author(s): Koyama T, Nakaoka Y, Fujio Y, Hirota H, Nishida K, Sugiyama S, Okamoto K, Yamauchi-Takihara K, Yoshimura M, Mochizuki S, Hori M, Hirano T, Mochizuki
  • Journal Title: J. Biol. Chem. 283 Pages: 24234-24244
• [Journal Article] Single Common Mutation in the Cardiac Sodium Channel Gene SCN5A with Diverse Clinical Phenotypes. (2008)
  • Author(s): Makita N, Behr E, Shimizu W, Horie M, Sunami A, Crotti L, Schulze-Bahr E, Fukuhara S, Mochizuki N, Makiyama N, Itoh H, Christiansen M, McKeown P, Miyamoto K, Kamakura S, Tsutsui H, Schwartz PJ, George Jr AL, Roden DM
  • Journal Title: J. Clin. Invest. 118 Pages: 2219-2229
• [Journal Article] Differential function of Tie2 at cell-cell contacts and cell-substratum contacts regulated by angiopoietin-1. (2008)
  • Author(s): Fukuhara S
  • Journal Title: Nat. Cell Biol. 10 Pages: 513-526
  • Peer Reviewed
• [Journal Article] Interaction of scaffolding adaptor protein Gab1 with tyrosine phosphatase SHP2 negatively regulates IGF-I-dependent myogenic differentiation via the ERK1/2 signaling pathway. (2008)
  • Author(s): Koyama T
  • Journal Title: J. Biol. Chem. 283 Pages: 24234-24244
  • Peer Reviewed
• [Journal Article] Spatial and temporal role of the apelin/APJ system in the caliber size regulation of blood vessels during angiogenesis. (2008)
  • Author(s): Kidoya H
  • Journal Title: EMBO J. 27 Pages: 522-534
  • Peer Reviewed
• [Journal Article] Conformational switch of angiotensin II type l receptor underlying mechanical stress-induced activation. (2008)
  • Author(s): Yasuda N
  • Journal Title: EMBO Rep 9 Pages: 179-186
  • Peer Reviewed
• [Journal Article] 15-lipoxygenase-1 in the vasculature : expanding roles in angiogenesis. (2008)
  • Author(s): Mochizuki N
  • Journal Title: Circ. Res. 102 Pages: 143-145
  • Peer Reviewed
• [Journal Article] Single Common Mutation in the Cardiac Sodium Channel Gene SCN5A with Diverse Clinical Phenotypes. (2008)
  • Author(s): Makita N
  • Journal Title: J. Clin. Invest. 118 Pages: 2219-2229
  • Peer Reviewed
• [Journal Article] Gab family proteins are essential for postnatal maintenance of cardiac function through transmitting neuregulin-1/ErbB signaling. (2007)
  • Author(s): Nakaoka Y, Nishida K, Narimatsu K, Kamiya A, Minami T, Sawa H, Okawa K, Fujio Y, Koyama T, 1 Maeda M, Sone M, Yamasaki S, Arai Y, Koh GY, Kodama T, Hirota H, Otsu K, Hirano T, Mochizuki N
  • Journal Title: J Clin. Invest 117 Pages: 1771-1181
• [Journal Article] A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart. (2007)
  • Author(s): Seguchi O, Takashima S, Yamazaki S, Asakura M, Asano Y, Shintani Y, Wakeno M, Minamino T, Kondo H, Furukawa H, Nakamaru K, Naito A, Takahashi T, Ohtsuka T, Kawakami K, Isomura T, Kitamura S, Tomoike H, Mochizuki N, Kitakaze M
  • Journal Title: J Clin. Invest 117 Pages: 2812-2824
• [Journal Article] Akt-PDK1 Complex Mediates EGF-induced Membrane Protrusion through Ral Activation. (2007)
  • Author(s): Yoshizaki H, Mochizuki N, Gotoh Y, Matsuda M
  • Journal Title: Mol Biol Cell 18 Pages: 119-128
• [Journal Article] Gab family proteins are essential for postnatal maintenance of cardisc function through transmitting neuregulin-1/ErbB s ignaling. (2007)
  • Author(s): Nakaoka Y.
  • Journal Title: J CIin.Invest 117 Pages: 1771-1181
  • Peer Reviewed
• [Journal Article] A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart. (2007)
  • Author(s): Seguchi O.
  • Journal Title: J Clin.Invest 117 Pages: 2812-2824
  • Peer Reviewed
• [Journal Article] Increased endoplasmic reticulum stress in atheroscierotic plaques associated with acute coronary syndrome. (2007)
  • Author(s): Myoishi M.
  • Journal Title: Circulation 116 Pages: 1226-1233
  • Peer Reviewed
• [Journal Article] Receptor activator of nuclear factor (NF)-{kappa}B ligand(RANKL) increases vascular permeability;Impaired permeability and angiogenesis in eNOS-deficient mice. (2007)
  • Author(s): Min JK
  • Journal Title: Blood 109 Pages: 1495-1502
  • Peer Reviewed
• [Journal Article] Akt-PDK1 Complex Mediates EGF-induced Membrane Protrusion through Ral Activation. (2007)
  • Author(s): Yoshizaki H
  • Journal Title: Mol Biol Cell 18 Pages: 119-128
• [Journal Article] Endophilin BAR domain drives membrane curvature by two newly identified structure-based mechanisms. (2006)
  • Author(s): Masuda M, Takeda S, Sone M, Ohki T, Mori H, Kamioka Y, Mochizuki N
  • Journal Title: EMBO J. 25 Pages: 2889-2897
• [Journal Article] Cardiac ischemia activates vascular endothelial cadherin promoter in both preexisting vascular cells and bone marrow cells involved in neovascularization. (2006)
  • Author(s): Kogata N, Arai Y, Pearson JT, Hashimoto K, Hidaka K, Koyama T, Somekawa S, Nakaoka Y, Ogawa M, Adams RH, Okada M, Mochizuki N
  • Journal Title: Circ Res. 98 Pages: 897-904
• [Journal Article] Vascular endothelial cadherin-mediated cell-cell adhesion regulated by a small GTPase (2006)
  • Author(s): Fukuhara S, Sakurai A, Yamagishi A, Sako K, Mochizuki N
  • Journal Title: Rap1. J Biochem. Mol. Biol. 39 Pages: 132-139
• [Journal Article] MAGI-1 is required for Rap1 activation upon cell-cell contact and for enhancement of VE-cadherin-mediated cell adhesion. (2006)
  • Author(s): Sakurai A, Fukuhara S, Yamagishi A, Sako K, Kamioka Y, Masuda M, Nakaoka Y, Mochizuki N
  • Journal Title: Mol. Biol. Cell 17 Pages: 966-976
• [Journal Article] Interaction of FoxO1 and TSC2 induces insulin resistance through activation of mTOR/p70S6K pathway. (2006)
  • Author(s): Cao Y
  • Journal Title: J. Biol. Chem. 281 Pages: 40242-40251
• [Journal Article] Endophilin BAR domain drives membrane curvature by two newly identified structure-based mechanisms. (2006)
  • Author(s): Masuda M
  • Journal Title: EMBO J. 25 Pages: 2889-2897
• [Journal Article] Cardiac ischemia activates vascular endothelial cadherin promoter in both preexisting vascular cells and bone marrow cells involved in neovascularization. (2006)
  • Author(s): Kogata N
  • Journal Title: Circ Res. 98 Pages: 897-904
• [Journal Article] Vascular endothelial cadherin-mediated cell-cell adhesion regulated by a small GTPase, Rapl. (2006)
  • Author(s): Fukuhara S
  • Journal Title: J Biochem. Mol. Biol. 39 Pages: 132-139
• [Journal Article] Involvement of adaptor protein Crk in malignant feature of human ovarian cancer cell line MCAS. (2006)
  • Author(s): Linguh H
  • Journal Title: Oncogene 25 Pages: 3547-3556
• [Journal Article] Involvement of adaptor protein Crk in malignant feature of human ovarian cancer cell line MCAS. (2005)
  • Author(s): Linguh H.
  • Journal Title: Oncogene (In press)
• [Journal Article] MAGI-1 is required for Rap1 activation upon cell-cell contact and for enhancement of VE-cadherin-mediated cell adhesion. (2005)
  • Author(s): Sakurai A.
  • Journal Title: Mol.Biol.Cell 17 Pages: 966-976
• [Journal Article] Enhanced functional Gap junction neoformation by RKA-dependent and Epac-Rap1-dependent signals downstream of cAMP in cardiac myocytes. (2005)
  • Author(s): Somekawa S.
  • Journal Title: Circ.Res. 92 Pages: 655-662
• [Journal Article] Long-term and sustained COMP-Ang1 induces long-lasting vascular enlargement and enhanced blood flow. (2005)
  • Author(s): Cho CH.
  • Journal Title: Circ Res. 97 Pages: 86-94
• [Journal Article] Local activation of Rap1 contributes to directional vascular endothelial cell migration accompanied by extension of microtubules on which RAPL, a Rap1-associating molecule, localizes. (2005)
  • Author(s): Fujita H.
  • Journal Title: J.Biol.Chem 280 Pages: 5022-5031
• [Journal Article] Cyclic AMP potentiates VE-cadherin-mediated cell-cell contact to enhance endothelial barrier function through Epac-Rap1 signaling pathway. (2005)
  • Author(s): Fukuhara S.
  • Journal Title: Mol.Cell Biol. 25 Pages: 136-146
• [Journal Article] ERK is an anti-inflammatory signal that suppresses expression of NF-kappaB-dependent inflammatory genes by inhibiting IKK activity in endothelial cells.
  • Author(s): Maeng YS.
  • Journal Title: Cell Signal (in press)
• [Presentation] Visualization of Fluorescence-marked Heart and blood vessel helps understanding of cardiovascular development during embryogenesis of living zebrafish (2010)
  • Author(s): Mochizuki N
  • Organizer: The 74th annual scientific meeting of the JCS
  • Place of Presentation: Kyoto International Conference Center
  • Year and Date: 2010-03-06
• [Presentation] a cyclic AMP-Epac-Rap1 pathway induces formation of circumferential actin bundles, which stabilize junctional VE-cadherin through a-/b-catenins. (2009)
  • Author(s): Noda K, Cho E, Fukuhara S, Mochizuki N
  • Organizer: 49th ASCB
  • Place of Presentation: San Diego
  • Year and Date: 2009-12-08
• [Presentation] A Rap1 small GTPase enhances VE-cadherin-dependent cell adhesion by inducing actin bundling at cell-cell contacts. (2009)
  • Author(s): Noda K, Cho E, Fukuhara S, Mochizuki N
  • Organizer: 第82回生化学会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-22
• [Presentation] 低分子量Gタンパク質Rap1は細胞間接着部位におけるアクチン線維の束化を介してVE-cadherin接着を増強する (2008)
  • Author(s): 野田一臣、張江暉、福原茂朋、桜井貴子、望月直樹
  • Organizer: 第31回分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Remarks]
  • URL: http://plaza.umin.ac.jp/ncvc/
• [Remarks]
  • URL: http://plaza.umin.ac.jp/ncvc/
• [Patent(Industrial Property Rights)] スフィンゴシン1-燐酸の新規トランスポーター分子 (2008)
  • Inventor(s): 望月直樹、川原敦雄、西毅、山口明人
  • Industrial Property Rights Holder: 国立循環器病センター、大阪大学
  • Industrial Property Number: 2008-245177
  • Filing Date: 2008-09-25