Role of phosphoinositide metabolism in cell polarity format

• Project/Area Number: 20013043
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: FUKAMI Kiyoko Tokyo University of Pharmacy and Life Science, 生命科学部, 教授 (40181242)
• Co-Investigator(Kenkyū-buntansha): KOUCHI Zen 東京薬科大学, 生命科学部, 研究員 (70322485)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥16,000,000 (Direct Cost: ¥16,000,000); Fiscal Year 2009: ¥8,000,000 (Direct Cost: ¥8,000,000); Fiscal Year 2008: ¥8,000,000 (Direct Cost: ¥8,000,000)
• Keywords: イノシトールリン脂質 / 細胞極性 / 浸潤突起形成 / ホスフォリパーゼC / 細胞運動 / 炎症

Research Abstract

We first examined the roles of PIP_2 in the invadopodia formation of human breast cancer cells. PIP2 accumulated at invadopodia, and injection of antibody against PIP2 blocked invadopodia formation. In addition, knockdown (KD) of PIP5KIa inhibited invadopodia formation. These results indicate that localized production of PIP2 by PIP5KIa is required for invadopodia formation and ECM degradation by human breast cancer cells.
On the other hand, we also found that the skin of PLCd1KO mice displays typical inflammatory phenotypes, including leukocyte infiltration, and expression of pro-inflammatory cytokines. We also detected that PLCd1KO mice had significantly elevated peripheral blood leukocytes compared to wild-type mice. These results indicate that lack of PLCd1 induces skin inflammation and systemic neutrophilia.

Research Products

• [Journal Article] Phospholipase C-eta2 is highly expressed in the habenula and retina. (2010)
  • Author(s): Kanemaru, K., Nakahara, M., Nakamura, Y., Hashiguchi, Y., Kouchi, Z., Yamaguchi, H., Oshima, N., Kiyonari, H., Fukami, K.
  • Journal Title: Gene Expr. Patterns 10 Pages: 119-126
  • Peer Reviewed
• [Journal Article] Phospholipase C-relatedbut catalytically inactive protein is required for insulin-induced cellsurface expression of g-aminobutyric acid type A receptors. (2010)
  • Author(s): Fujii, M., Kanematsu, T., Ishibashi, H., Fukami, K., Takenawa, T., Nakayama, K.I., Moss, S.J., Nabekura, J., Hirata. M.
  • Journal Title: J. Biol. Chem. 285 Pages: 4837-46
  • Peer Reviewed
• [Journal Article] Phospholipase C-eta2 is highly expressed in the habenula and r etina. (2010)
  • Author(s): Kanemaru, K., et al.
  • Journal Title: Gene Expr.Patterns. 10 Pages: 119-126
  • Peer Reviewed
• [Journal Article] Involvement of phospholipase C-related inactive protein in the reproductive system through the regulation of gonadotropin levels. (2009)
  • Author(s): Matsuda, M., Tsutsumi, K., Kanematsu, T., Fukami, K., Terada, Y., Takenawa, T., Nakayama, K.I., Hirata, M.
  • Journal Title: Biology of Reproduction. 81 Pages: 681-689
  • Peer Reviewed
• [Journal Article] MARCKS regulateslamellipodia formation induced by IGF-I via association with PIP2 and beta-actin at membrane microdomains. (2009)
  • Author(s): Yamaguchi, H., Shiraishi, M., Fukami, K., Tanabe, A., Ikeda-Matsuo, Y., Naito, Y., Sasaki, Y.
  • Journal Title: J. Cell. Physiol. 220 Pages: 748-55
  • Peer Reviewed
• [Journal Article] Lipid rafts and caveolin-1 are required forinvadopodia formation and extracellular matrix degradation by human breast cancer cells. (2009)
  • Author(s): Yamaguchi, H., Takeo, Y., Yoshida, S., Kouchi, Z., Nakamura, Y., Fukami, K.
  • Journal Title: Cancer Res 69 Pages: 8594-8602
  • Peer Reviewed
• [Journal Article] Illuminatingcell-cycle progression in the developing zebrafish embryo. (2009)
  • Author(s): Sugiyama, M., Sakaue-Sawano, A., Iimura, T., Fukami, K., Kitaguchi, T., Kawakami, K., Okamoto, H., Higashijima, S., Miyawaki, A.
  • Journal Title: Proc. Natl. Acad. Sci. USA 106 Pages: 20812-20817
  • Peer Reviewed
• [Journal Article] p120 catenin recruits cadherins to gamma-secretase and inhibits production of Abeta peptide. (2009)
  • Author(s): Kouchi, Z., Barthet, G., Serban, G., Georgakopoulos, A., Shioi, J., Robakis, N.K.
  • Journal Title: J. Biol. Chem. 284 Pages: 1954-61
  • Peer Reviewed
• [Journal Article] Lipid rafts and caveolin-1 are required for invadopodia formation and extracellular matrix degradation by human breast cancer cells. (2009)
  • Author(s): Yamaguchi,H., et al.
  • Journal Title: Cancer Res. 69 Pages: 8594-8602
  • Peer Reviewed
• [Journal Article] Phospholipase C-d1 is an essential molecule downstream of Foxn1 the gene responsible for the nude mutation, in normal hair development. (2008)
  • Author(s): Nakamura, Y., Ichinohe, M., Hirata, M., Matsuura, H., Fujiwara, T., Igarashi, T., Nakahara, M., Yamaguchi, H., Yasugi, S., Takenawa, T., Fukami, K.
  • Journal Title: FASEB J. 22 Pages: 841-849
  • Peer Reviewed
• [Journal Article] Mechanisms of depolarization-induced endocannabinoid release: Pharmacological and genetic approach. (2008)
  • Author(s): Hashimotodani, Y., Ohno-Shosaku, T., Maejima, T., Fukami, K., Kano, M.
  • Journal Title: Neuropharmacology 54 Pages: 58-67
  • Peer Reviewed
• [Journal Article] Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. (2008)
  • Author(s): Sakaue-Sawano, A., Kurokawa, H., Morimura, T., Hanyu, A., Hama, H., Osawa, H., Kashiwagi, S., Fukami, K., Miyata, T., Miyoshi, H., Imamura, T., Ogawa, M., Masai, H., Miyawaki, A.
  • Journal Title: Cell 132 Pages: 341-343
  • Peer Reviewed
• [Journal Article] Reduced fertility of mouse epididymal sperm lacking Prss21/Tesp5 is rescued by sperm exposure to uterine microenvironment. (2008)
  • Author(s): Yamashita, M., Honda, A., Ogura, A., Kashiwabara, S Fukami, K., Baba, T.
  • Journal Title: Genes Cells. 10 Pages: 1001-13
  • Peer Reviewed
• [Journal Article] DominiqueSimon-Chazottes, Jean-Louis Guenet, Thomas Franz, Alopecia and male infertility in oligotriche mutant miceare caused by a deletion on distal chromosome 9. (2008)
  • Author(s): Runkel1, F., Aubin, I., Bussow, H., Fukami, K., Nakamura, Y.
  • Journal Title: Mamm. G enome. 19 Pages: 691-702
  • Peer Reviewed
• [Journal Article] Phospholipase Cδ1 is an essential molecule downstream of Foxn1, the gene regpongihle for the nude mutation, innormal hair development (2008)
  • Author(s): Nakamura Y., et.al.
  • Journal Title: FASEB J 22 Pages: 841-849
  • Peer Reviewed
• [Journal Article] Vlsualizing spatiotemporal dynamics of multiceliular cell-cycle progression (2008)
  • Author(s): Sakaue-Sawano A., et.al.
  • Journal Title: Cell 132 Pages: 341-343
  • Peer Reviewed
• [Journal Article] Reduced fbrtility of mousu epididymal sperm lacking Prss21/Tesp 5 is rescued by sperm exposure to uterine microenvironment (2008)
  • Author(s): Yamashita. M, et.al.
  • Journal Title: Genes Cell 10 Pages: 1001-1013
  • Peer Reviewed
• [Journal Article] Calcium fluxes cause the nuclear shrinkage and translocation of phospholipase C-d1 into the nucleus.
  • Author(s): Okada, M., Taguchi, K., Maekawa, S., Fukami, K., Yagisawa, H.
  • Journal Title: Neurosci. Lett. (in press)
  • Peer Reviewed
• [Journal Article] Phosphatidylinositol 4, 5-bisphosphate and PIP5-kinase Ia are required for invadopodia formation in human breast cancer cells.
  • Author(s): Yamaguchi, H., Yoshida, S., Muroi, E., Kawamura, M., Kouchi, Z., Nakamura, Y., Sakai, R., Fukami, K.
  • Journal Title: Cancer Sci (in press)
  • Peer Reviewed
• [Journal Article] GABAA receptor subunit alteration-dependent diazepam insensitivity in the cerebellum of phospholipase C- related inactive protein knockout mice.
  • Author(s): Mizokami, A., Tanaka, H., Ishibashi, H., Umebayashi, H., Fukami, K., Takenawa, T., Nakayama, K.I., Yokoyama, T., Nabekura, J., Kanematsu, T., Hirata, M.
  • Journal Title: J. Neurochemistry (in press)
  • Peer Reviewed
• [Journal Article] Phosphatidylinositol 4,5-bisphosphate and PIP5-kinase Ia are required for invadopodia formation in human breast cancer cells.
  • Author(s): Yamaguchi, H., et al.
  • Journal Title: Cancer Sci. (in press)
  • Peer Reviewed
• [Presentation] ホスフォリパーゼCδ1は様々な生理機能に関与する (2009)
  • Author(s): 深見希代子
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-21
• [Presentation] Phospholipase C-delta1 Regulates Hair Keratin Expression And Hair Shaft Formation Downstream of Foxn1 (2009)
  • Author(s): Nakamura, Y., Ichinohe, M., Takahashi, S., Inanobe, S., Kanemaru, K., Fukami, K.
  • Organizer: The American Society for Cell Biology 49th Annual meeting
  • Place of Presentation: San Diego
• [Presentation] The interaction of hTERT and nucleolar GTP-binding protein GNL3L and Nucleostenmin regulates tumor initiating cell behavior (2009)
  • Author(s): 岡本奈緒子、安川麻美、毎田佳子、工富知子、深見希代子、William C. Hahn、増富健吉
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Physiological functions of phospholipase Cδ1 in adipose tissue development and obesity (2009)
  • Author(s): Ishii, R., Hirata, M., Suzuki, M., Matsuoka, S., Nakamura, Y., kouchi, Z., Yamaguchi, H., Sasaki, T., Kitamurea, T., Fukami, K
  • Organizer: The 6th Japan-Korea Conference on celluer signaling for young scientists
  • Place of Presentation: Nagasaki
• [Presentation] Phospholipase Cδ3 is involved in neurite outgrowth of cerebral cortical neurons and Neuro2A cells (2009)
  • Author(s): Shibayama, N., Kouchi, Z., Fukuda, T., Igrashi, T., Nakamura, Y., p Yamaguchi, H., Yanagi, S., Fukami, K.
  • Organizer: The 6th Japan-Korea Conference on Cellular Signaling for Young Scientists
  • Place of Presentation: Nagasaki
• [Presentation] Lack of phospholipase C delta1 accelerates skin wound healing (2009)
  • Author(s): Inanobe, S., Nakamura, Y., Ichinohe, M., Hirata, M., Kouchi, Z., Yamaguchi, H., Fukami, K.
  • Organizer: The 6th Japan-Korea Conference on Cellular Signaling for Young Scientists
  • Place of Presentation: Nagasaki
• [Presentation] Illuminating Cell-Cycle Progression Inside Developing Zebrafish Embryo -A novel insight of early skeletogenesis (2009)
  • Author(s): Sugiyama, M., Sakaue-Sawano, A., Iimura, T., Fukami, K., Kitaguchi, T., Kawakami, K., Okamoto, H., Higashijima, S., Miyawaki, A.
  • Organizer: The 26th Naito Conference on Osteobiology
  • Place of Presentation: Awaji
• [Presentation] ホスフォリパーゼCδ1は様々な生理機能に関与する (2009)
  • Author(s): 深見希代子、平田真之、石井里佳、一戸学、中村由和
  • Organizer: 第82回日本生化学会大会シンポジウム
  • Place of Presentation: 神戸
• [Presentation] 大腸癌細胞におけるvitaminDレセプター依存的なE-cadherinの発現誘導にPIP kinase IIβが関与する (2009)
  • Author(s): 河内全、小堀真平、宮崎聡一郎、中村由和、山口英樹、深見希代子
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] 脂肪細胞形成におけるホスホリパーゼCδ1の生理機能解析 (2009)
  • Author(s): 石井里佳、平田真之、鈴木睦実、松岡翔一、中村由和、河内全、山口英樹、深見希代子
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] PLCδ1による毛包形態および毛の構成ケラチン発現の制御 (2009)
  • Author(s): 高橋佐織、一戸学、中村由和、平田真之、河内全、山口英樹、深見希代子
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] 白血球の機能、分化におけるホスホリパーゼδ1の機能解析 (2009)
  • Author(s): 金丸佳織、中村由和、河内全、山口英樹、深見希代子
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] リン脂質代謝が創る生命のしくみ (2009)
  • Author(s): 深見希代子
  • Organizer: 岐阜薬科大学東京支部総会シンポジウム
  • Place of Presentation: 東京
• [Presentation] hTERTと核小体GTP結合タンパク質GNL3L/NSは腫瘍形成能を制御する (2009)
  • Author(s): 岡本奈緒子、安川麻美、毎田佳子、工富知子、深見希代子、William C. Hahn、増富健吉
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Neuro2a細胞の神経突起伸長におけるPLCδ3の機能解析 (2009)
  • Author(s): 河内全、五十嵐隆公、柴山奈美、中原真道、中村由和、山口英樹、深見希代子
  • Organizer: 第51回日本脂質生化学会
  • Place of Presentation: 名古屋
• [Presentation] 創傷治癒におけるホスポリパーゼCd1の役割 (2009)
  • Author(s): 稲野邊俊一、中村由和、一戸学、平田真之、河内全、山口英樹、深見希代子
  • Organizer: 第51回日本脂質生化学会
  • Place of Presentation: 名古屋
• [Presentation] 肥満におけるホスホリパーゼCdeltalの生理機能解析 (2009)
  • Author(s): 平田真之、石井里佳、一戸学、中村由和、河内全、山口英樹、深見希代子
  • Organizer: 第51回日本脂質生化学会
  • Place of Presentation: 名古屋
• [Presentation] 浸潤突起形成における脂質ラフトとカベオリンの役割 (2009)
  • Author(s): 山口英樹、竹尾由希子、吉田周平、河内全、中村由和、深見希代子
  • Organizer: 第61回日本細胞生物学会
  • Place of Presentation: 名古屋
• [Presentation] Phospholipase C・3はNeuro2a細胞における神経突起伸長に関与する (2009)
  • Author(s): 柴山奈美、河内全、五十嵐隆公、中村由和、山口英樹、深見希代子
  • Organizer: 第61回日本細胞生物学会大会
  • Place of Presentation: 名古屋
• [Presentation] がん発生メカニズム (2009)
  • Author(s): 深見希代子
  • Organizer: 東京医大がん専門薬剤師に対する研修
  • Place of Presentation: 東京
• [Presentation] ホスフォリパーゼCδ1を介した毛包形成と表皮恒常性維持のメカニズム (2008)
  • Author(s): 深見希代子
  • Organizer: 日本生化学会、分子生化学会合同年会(BMB)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] ホスフォリパーゼCd1を介した毛包形成と表皮恒常性維持のメカニズム (2008)
  • Author(s): 深見希代子
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] ホスホリパーゼCδ3はNeuro2a細胞における神経突起伸長に関与する (2008)
  • Author(s): 河内全、五十嵐隆公、中原真道、柴山奈美、中村由和、山口英樹、深見希代子
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] 浸潤突起形成におけるイノシトールリン脂質の役割 (2008)
  • Author(s): 山口英樹、深見希代子
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] 創傷治癒におけるPhospholipase Cδ1の役割 (2008)
  • Author(s): 稲野邊俊一、一戸学、中村由和、平田真之、河内全、山口英樹、深見希代子
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] yosinVIの膜輸送機能におけるホスフォリパーゼCδ3の関与 (2008)
  • Author(s): 桜井和之、平田真之、石井里佳、中村由和、河内全、山口英樹、深見希代子
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] C3H10T1/2間葉系幹細胞の脂肪細胞分化におけるPLCdelta1の関与 (2008)
  • Author(s): 平田真之、一戸学、桜井和之、中村由和、河内全、山口英樹、深見希代子
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] Phospholipase C-delta1はFoxn1下流で体毛形成に関与する (2008)
  • Author(s): 一戸学、中村由和、平田真之、山口英樹、深見希代子
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] Phospholipase C-delta1 is an essential molecule downstream of Foxn1, the gene responsible for nude mutation, in normal hair development. (2008)
  • Author(s): Ichinohe, M., Nakamura, Y., Hirata, M., Yamaguchi, H., Fukami, K.
  • Organizer: The 33rd FEBS Congress & 11t IUBMB Conference
  • Place of Presentation: Athens, Greece
• [Presentation] The effect of phospholipase C-delta 1 on differentiation of C3H10T1/2 mesenchymal cell line into adipocytes and chondrocytes (2008)
  • Author(s): Hirata, M., Ichinohe, M., Sakurai, K., Nakamura, Y., Kouchi, Z., Yamaguchi, H., Fukami, K.
  • Organizer: 33rd FEBS Congress & 11th IUBMB Conference
  • Place of Presentation: Athens, Greece
• [Presentation] Phospholipase Cd3はNeuro2a細胞における神経突起伸長に関与する (2008)
  • Author(s): 河内全、五十嵐隆公、中村由和、山口英樹、深見希代子
  • Organizer: 第60回日本細胞生物学会大会
  • Place of Presentation: 横浜
• [Presentation] Fucciトランスジェニックマウスを用いた組織発生における細胞周期の解析 (2008)
  • Author(s): 黒川裕、阪上-沢野朝子、深見希代子、濱裕、宮脇敦史
  • Organizer: 第60回日本細胞生物学会
  • Place of Presentation: 横浜
• [Presentation] 創傷治癒におけるホスホリパーゼCδ1の役割 (2008)
  • Author(s): 稲野辺俊一、一戸学、中村由和、平田真之、河内全、山口英樹、深見希代子
  • Organizer: 第60回日本細胞生物学会
  • Place of Presentation: 横浜
• [Presentation] Phospholipase Cd3はmyosinViと結合し内耳有毛細胞において共発現する (2008)
  • Author(s): 櫻井和之、平田真之、中村由和、河内全、山口英樹、深見希代子
  • Organizer: 第60回日本細胞生物学会
  • Place of Presentation: 横浜
• [Presentation] 浸潤性乳癌細胞における浸潤突起形成の分子機構. (2008)
  • Author(s): 山口英樹、深見希代子
  • Organizer: 第60回日本細胞生物学会
  • Place of Presentation: 横浜
• [Presentation] PLCd3はNeuro2a細胞における神経突起伸長に関与する (2008)
  • Author(s): 河内全、五十嵐隆公、中原真道、中村由和、山口英樹、深見希代子
  • Organizer: 第50回日本脂質生化学会
  • Place of Presentation: 徳島
• [Presentation] Phospholipase Cd1はFoxn1下流で体毛形成に関与する (2008)
  • Author(s): 一戸学、中村由和、山口英樹、深見希代子
  • Organizer: 第50回日本脂質生化学会
  • Place of Presentation: 徳島
• [Presentation] Mouse Sperm Lacking Serine Protease Prss21/Tesp5 Barely Undergo the Zona Pellucida-Induced Acrosome Reaction, but Do Fertilize the Egg. (2008)
  • Author(s): Yamashita, M., Honda. A, Agura. A., Kashiwabara. S., Fukami. K., Baba. T.
  • Organizer: First World Congress on Reproductive Biology
  • Place of Presentation: Hawaii
• [Book] Roles of phospholipase C isozymes in organogenesis and embryonic development (2009)
  • Author(s): Nakamura, Y., Fukami, K.
• [Book] Physiology (2009)
  • Author(s): Nakamura. Y., et al.
  • Total Pages: 10
  • Publisher: Int.Union Physiol.Sci./Am.Physiol.Soc
• [Book] Advan. Enzyme Regul (2008)
  • Author(s): Fukami, K., Ichinohe, M., Hirata, M., Nakamura, Y
• [Book] BMB Rep (2008)
  • Author(s): Suh P.G., et.al.
  • Publisher: Multiple roles of phosphoinositide-specific phospholipase C isozymes
• [Book] Clinical Neuroscience
  • Author(s): 河内全
  • Publisher: 中外医学社