Spatial and temporal regulation of signalling molecules by phosphoinositides

2010 Fiscal Year Final Research Report

• Project/Area Number: 18GS0312
• Research Category: Grant-in-Aid for Creative Scientific Research
• Allocation Type: Single-year Grants
• Research Institution: Kobe University (2007-2010); The University of Tokyo (2006)
• Principal Investigator: TAKENAWA Tadaomi 神戸大学, 大学院・医学研究科, 特命教授 (40101315)
• Co-Investigator(Kenkyū-buntansha): SASAKI Takehiko 秋田大学, 大学院・医学系研究科, 教授 (50333365)
• Co-Investigator(Renkei-kenkyūsha): ITOH Toshiki 神戸大学, 大学院・医学研究科, 准教授 (30313092) ; IJUIN Takeshi 神戸大学, 大学院・医学研究科, 助教 (00361626) ; YAMAZAKI Daisuke 神戸大学, 大学院・医学研究科, 助教 (50422415)
• Project Period (FY): 2006 – 2010
• Keywords: ホスホイノシタイド / 細胞内情報伝達 / 脂質結合蛋白質 / 膜変形作用

Research Abstract

We developed a new method to quantify and visualize phosphoinositides by the use of Q-dot labeled PH domains which recognize phosphoinositides with high affinity and specificity. By this method, three different phosphoinositides were quantified and visualized simultaneously. We found that FBP17 and CIP4 proteins have F-Bar domains that bind phosphoinositides and deform membranes. F-Bar domain forms a polymerized filament and changes plasma membrane to tube-like structure, resulting in the formation of invaginated pits. We also found a new phosphoinositide binding domain, SYLF domain in SH3YL1, which was involved in the formation of macropinocytosis.

Research Products

• [Journal Article] Regulation of insulin signalling and glucose transporter 4(GLUT4) exocytosis by the phosphatidylinositol 3, 4, 5-trisphosphate(PIP3) phosphatase, SKIP (2012)
  • Author(s): Ijuin, T., Takenawa, T
  • Journal Title: J Biol Chem
  • Peer Reviewed
• [Journal Article] Quantification and visualization of phosphoinositides by quantum dot-labeled specific binding-domain probes (2012)
  • Author(s): Irino, Y., Tokuda, E., Hasegawa, J., Itoh, T., Takenawa, T
  • Journal Title: J Lipid Res
  • Peer Reviewed
• [Journal Article] SH3YL1 regulates dorsal ruffle formation by a novel phosphoinositide-binding domain (2011)
  • Author(s): Hasegawa, J., Tokuda, E., Tenno, T., Tsujita, K., Sawai, H., Hiroaki, H., Takenawa, T., Itoh, T
  • Journal Title: J. Cell Biol Volume: 193 Pages: 901-916
  • Peer Reviewed
• [Journal Article] Proteome of acidic phospholipid-binding proteins : Spatial and temporal regulation of coronin 1A by phosphoinositid (2010)
  • Author(s): Tsujita, K., Itoh, T., Kondo, A., Oyama, M., Kozuka-Hata, H., Irino, Y., Hasegawa, J., and Takenawa, T
  • Journal Title: J Biol Chem Volume: 285 Pages: 6781-6789
  • Peer Reviewed
• [Journal Article] GABA(A) receptor subunit alteration-dependent diazepam insensitivity in the cerebellum of phospholipase C-related inactive protein knockout mice (2010)
  • Author(s): Mizokami, A., Tanaka, H., Ishibashi, H., Umebayashi, H., Fukami, K., Takenawa, T., Nakayama, KI., Yokoyama, T., Nabekura, J., Kanematsu, T., and Hirata, M
  • Journal Title: J Neurochem Volume: 114 Pages: 302-310
  • Peer Reviewed
• [Journal Article] Phosphoinositide-binding interface proteins involved in shaping cell membranes (2010)
  • Author(s): Takenawa, T
  • Journal Title: Proc Jpn Acad Ser B Phys Biol Sci Volume: 86 Pages: 509-523
  • Peer Reviewed
• [Journal Article] WASP and WAVE family proteins : Friends or foes in cancer invasion (2010)
  • Author(s): Kurisu, S., and Takenawa, T
  • Journal Title: Cancer Sci Volume: 101 Pages: 2093-2104
  • Peer Reviewed
• [Journal Article] Nebulin and N-WASP cooperate to cause IGF1-induced sarcomeric actin filament formation (2010)
  • Author(s): Takano, K., Takano, H., Suetsugu, S., Kurita, S., Tsujita, K., Kimura, S., Karatsu, T., Takenawa, T., and Endo, T
  • Journal Title: Science Volume: 330 Pages: 1536-1540
  • Peer Reviewed
• [Journal Article] The PtdIns(3, 4) P2 phosphatase INPP4A is a suppressor of excitotoxic neuronal death (2010)
  • Author(s): Sasaki, J., Kofuji, S., Itoh, R., Momiyama, T., Takayama, K., Murakami, H., Chida, S., Tsuya, Y., Takasuga, S., Eguchi, S., Asanuma, K., Horie, Y., Miura, K., Davies, EM., Mitchell, C., Yamazaki, M., Hirai, H., Takenawa, T., Suzuki, A., and Sasaki, T
  • Journal Title: Nature Volume: 465 Pages: 497-501
  • Peer Reviewed
• [Journal Article] The tyrosine kinase Fer is a downstream target of the PLD-PA pathway that regulates cell migration (2009)
  • Author(s): Itoh, T., Hasegawa, J., Tsujita, K., Kanaho, Y., and Takenawa, T
  • Journal Title: Sci Signal Volume: 2 Pages: 52
  • Peer Reviewed
• [Journal Article] Sac3 is an insulin-regulated phosphatidylinositol 3, 5-bisphosphate phosphatase : gain in insulin responsiveness through Sac3 down-regulation in adipocytes (2009)
  • Author(s): Ikonomov, OC., Sbrissa, D., Ijuin, T., Takenawa, T., and Shisheva, A
  • Journal Title: J. Biol. Chem Volume: 284 Pages: 23961-23971
  • Peer Reviewed
• [Journal Article] Involvement of Rac and Rho signaling in cancer cell motility in 3D substrates (2009)
  • Author(s): Yamazaki, D., Kurisu, S., and Takenawa, T
  • Journal Title: Oncogene Volume: 28 Pages: 1570-1583
  • Peer Reviewed
• [Journal Article] A distinct pool of phosphatidylinositol 4, 5-bisphosphate in caveolae revealed by a nanoscale labeling technique (2009)
  • Author(s): Fujita, A., Cheng, J., Tauchi-Sato, K., Takenawa, T., and Fujimoto, T
  • Journal Title: Proc Natl Acad Sci USA Volume: 106 Pages: 9256-9261
  • Peer Reviewed
• [Journal Article] Sequential Regulation of DOCK2 Dynamics by Two Phospholipids during Neutrophil Chemotaxis (2009)
  • Author(s): Kunisaki, Y., Sasaki, T.(16名中14番), Fukui, Y.
  • Journal Title: Science Volume: 17 Pages: 384-387
  • Peer Reviewed
• [Journal Article] Involvement of proton-sensing TDAG8 in extracellular acidification-induced inhibition of proinflammatory cytokine production in peritoneal macrophages (2009)
  • Author(s): Mogi, C., Sasaki, T.(14名中9番), Okajima, F.
  • Journal Title: J. Immunol Volume: 182 Pages: 3243-3251
  • Peer Reviewed
• [Journal Article] Increased insulin action in SKIP heterozygous knockout mice (2008)
  • Author(s): Ijuin, T., Yu, Y. E., Mizutani, K., Pao, A., Tateya, S., Tamori, Y., Bradley, A., and Takenawa, T
  • Journal Title: Mol. Cell Biol Volume: 28 Pages: 5184-5195
  • Peer Reviewed
• [Journal Article] Sequential signals toward podosome formation in NIH-src cells (2008)
  • Author(s): Oikawa, T., Itoh, T., Takenawa, T
  • Journal Title: J. Cell Biol Volume: 182 Pages: 157-169
  • Peer Reviewed
• [Journal Article] Involvement of the nectin-afadin complex in PDGF-induced cell survival (2008)
  • Author(s): Kanzaki, N., Ogita, H., Komura, H., Ozaki, M., Sakamoto, Y., Majima, T., Ijuin, T., Takenawa, T., and Takai, Y.
  • Journal Title: Involvement of the nectin-afadin complex in PDGF-induced cell survival Volume: 121 Pages: 2008-2017
  • Peer Reviewed
• [Journal Article] CD28 provides T cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer (2008)
  • Author(s): Garcon, F., Sasaki, T.(7名中6番), Okkenhaug, K.
  • Journal Title: Blood Volume: 111 Pages: 1464-1471
  • Peer Reviewed
• [Journal Article] Effective clearance of intracellular Leishmania major in vivo requires Pten in macrophages (2008)
  • Author(s): Kuroda, S., T., Sasaki, T.(14名中3番), Suzuki, A.
  • Journal Title: Eur J. Immunol Volume: 38 Pages: 1131-1140
  • Peer Reviewed
• [Journal Article] A voltage-sensing phosphatase, Ci-VSP, which shares sequence identity with PTEN dephosphorylates phosphatidylinositol 4, 5-bisphosphate (2008)
  • Author(s): Iwasaki, H., Sasaki, T.(9名中8番), Okamura, Y.
  • Journal Title: Proc. Natl. Acad. Sci Volume: 105 Pages: 7970-7975
  • Peer Reviewed
• [Journal Article] Critical roles of the p110βsubtype of phosphoinositide 3-kinase in lipopolysaccharide-induced Akt activation and negative regulation of nitrite production in RAW 264. 7 cells (2008)
  • Author(s): Tsukamoto, K., Sasaki, T.(7名中6番), Hazeki, O.
  • Journal Title: J. Immunol Volume: 180 Pages: 2054-2061
  • Peer Reviewed
• [Journal Article] Loss of PIP5KIγ, unlike other PIP5KI isoforms, impairs the integrity of the membrane cytoskeleton in murine megakaryocytes (2008)
  • Author(s): Wang, Y., Sasaki, T.(13名中9番), Abrams, C.
  • Journal Title: J. Clin. Invest Volume: 118 Pages: 812-819
  • Peer Reviewed
• [Journal Article] Pten deficiency in melanocytes results in resistance to hair graying and susceptibility to carcinogen-induced melanomagenesis (2008)
  • Author(s): Inoue-Narita, T., Sasaki, T.(18名中3番), Suzuki, A.
  • Journal Title: Cancer Res Volume: 68 Pages: 5760-5768
  • Peer Reviewed
• [Journal Article] The PI3 kinase.-Akt pathway mediates renal tubular injury induced by cisplatin nephrotoxicity (2008)
  • Author(s): Terada, Y., Sasaki, T.(8名中7番), Sasaki, S.
  • Journal Title: Kidney Int Volume: 180 Pages: 430-445
  • Peer Reviewed
• [Journal Article] IGF-I secreted by osteoblasts acts as a poteint chemotactic factor for osteoblast (2008)
  • Author(s): Nakasaki, M., Sasaki, T.(6名中4番), Itoh, K.
  • Journal Title: Bone Volume: 43 Pages: 869-879
  • Peer Reviewed
• [Journal Article] Loss of PIP5KI. demonstrates that PIP5KI isoform-specific PIP2 synthesis is required for IP3 formation (2008)
  • Author(s): Wang, Y., Sasaki, T.(10名中6番), Abrams, C.
  • Journal Title: Proc. Natl. Acad. Sci Volume: 105 Pages: 14064-14069
  • Peer Reviewed
• [Journal Article] SGIP1alpha is an endocytic protein that directly interacts with phospholipids and Eps15 (2007)
  • Author(s): Uezu, A., Horiuchi, A., Kanda, K., Kikuchi, N., Umeda, K., Tsujita, K., Suetsugu, S., Araki, N., Yamamoto, H., Takenawa, T., and Nakanishi, H.
  • Journal Title: J. Biol. Chem Volume: 282 Pages: 26481-26489
  • Peer Reviewed
• [Journal Article] Core protein machinery for mammalian PtdIns(3, 5) P2 synthesis and turnover that regulates the progression of endosomal transport : Novel Sac phosphatase joins the ArPIKfyve-PIKfyve complex (2007)
  • Author(s): Sbrissa, D., Ikonomov, OC., Fu, Z., Ijuin, T., Gruenberg, J., Takenawa, T., and Shisheva, A.
  • Journal Title: J. Biol. Chem Volume: 282 Pages: 23878-23891
  • Peer Reviewed
• [Journal Article] DA-Raf1, a competent intrinsic dominant-negative antagonist of the Ras-ERK pathway, is required for myogenic differentiation (2007)
  • Author(s): Yokoyama, T., Takano, K., Yoshida, A., Katada, F., Sun, P., Takenawa, T., Andoh, T., and Endo, T.
  • Journal Title: J. Cell Biol Volume: 177 Pages: 781-793
  • Peer Reviewed
• [Journal Article] Curved EFC/F-Bar domein dimmers are jointed end to end into a filasment for membrane invagination in endocytosis Cell (2007)
  • Author(s): Shimada, A., Niwa, H., Tsujita, K., Suetsugu, S., Nitta, K., Hanawa-Suetsugu, K., Azkasaka, R., Nishino, Y., Toyama, M., Chen, L., Sugano, S., Shirouzu, M., Nagayama, K., * Takenawa, T., and* Yokoyama, S.
  • Volume: 129
  • Pages: 761-772
  • Peer Reviewed
• [Journal Article] The WASP-WAVE protein network : connecting the membrane to the cytoskeleton (2007)
  • Author(s): Takenawa, T., and Suetsugu, S.
  • Journal Title: Nature Rev. Mol. Cell Biol Volume: 8 Pages: 37-48
  • Peer Reviewed
• [Journal Article] Rac-WAVE-mediated actin reorganization is required for organization and maintenance of cell-cell adhesion (2007)
  • Author(s): Yamazaki, D., Oikawa, T., and Takenawa, T.
  • Journal Title: J. Cell Sci Volume: 120 Pages: 86-100
  • Peer Reviewed
• [Journal Article] Regulation of FcγR-stimulated phagocytosis by the 72 kDa inositol polyphosphate 5-phosphatase (2007)
  • Author(s): Horan, K., Sasaki, T.(7名中6番), Mitchell, C.
  • Journal Title: Blood Volume: 110 Pages: 4480-4491
  • Peer Reviewed
• [Journal Article] Control of cell polarity and motility by the PI(3, 4, 5) P3 phosphatase SHIP1 (2007)
  • Author(s): Nishio, M., Sasaki, T.(19名中19番)
  • Journal Title: SHIP1 Volume: 9 Pages: 36-44
  • Peer Reviewed
• [Presentation] Interface proteins between membrane and actin cytoskeleton (2010)
  • Author(s): Takenawa, T.
  • Organizer: CNIC Seminar
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2010-03-15
• [Presentation] Phosphoinositide-binding proteins that induce membrane deformation (2009)
  • Author(s): Takenawa, T.
  • Organizer: Second International Conference on F-BAR Proteins
  • Place of Presentation: Stockfolm, Sweeden
  • Year and Date: 20091001-03
• [Presentation] WASP/WAVE proteins are involved ion invasion and metastasis of cancer cells (2008)
  • Author(s): Takenawa, T.
  • Organizer: Physiological Meeting
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20081022-23
• [Presentation] Phosphoinositide-binding proteins that induce membrane deformation with N-WASP/WAVE proteins (2008)
  • Author(s): Takenawa, T.
  • Organizer: 2nd Singapore Lipid Symposium
  • Place of Presentation: National University of Singapore
  • Year and Date: 20080305-07
• [Presentation] WAVEs regulate lamellipodia formation and the movement 0f cancer cells with high Rac activity (2007)
  • Author(s): Takenawa, T.
  • Organizer: 4th international Symposium on Functional molecules linked to neurodegeneration and oncogenesis
  • Place of Presentation: Nagoya
  • Year and Date: 20071025-26
• [Presentation] Specific regulation of insulin signaling in skeletal muscle by the PIP3 phosphatase, SKIP (2006)
  • Author(s): Ijuin, T., Takenawa, T.
  • Organizer: 2nd International Symposium on the 21st century COE program
  • Place of Presentation: Akita Univ, School of Medicine, Akita
  • Year and Date: 20060623-25