Mechanism of hair follicle formation regulated by Phosphoinositide metabolism

• Project/Area Number: 19370057
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• 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): YAMAGUCHI Hideki 東京薬科大学, 生命科学部, 講師 (10345035)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2008: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2007: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
• Keywords: イノシトールリン脂質 / 表皮と毛包形成 / ホスフォリパーゼC / ヌードマウス / 毛形成 / ホスフォリパーゼ C / Foxn1 / ヘアケラチン

Research Abstract

我々はPhospholipase C d1(PLC d1)の遺伝子欠損(KO)マウスを作製し、PLCd1KOマウスが毛包の形態異常を伴う顕著な体毛の減少を示すことを報告してきた。今回PLCd1KOマウスとよく似たマウスとして転写因子Foxn1が先天的に変異しているヌードマウスに着目した。ヌードマウスでは、毛を構成する主なヘアケラチンの一つであるmHa3遺伝子の発現が低下し、無毛となる。PLCd1KOマウス体毛減少のメカニズムを詳細に検討した所、ヌードマウスと同様にPLCd1KOマウスの皮膚においてもmHa3遺伝子の発現が低下していた。またヌードマウス皮膚では、PLCd1の発現が低下していた。こうした結果は、毛包形成において、Foxn1→PLCd1→mHa3というシグナルの流れが存在していることを示している。

Research Products

• [Journal Article] Phospholipase C-d1 is an essential molecule downstream of Foxn1, the gene responsible for the nude mutation (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: in normal hair development. FASEB J. 22 Pages: 841-849
• [Journal Article] Membrane targeting of WAVE2 is not sufficient for WAVE2 dependent actin polymerization : a role for IRSp53 in mediating the interaction between Rac and WAVE2 (2008)
  • Author(s): Abou-Kheir, W., Issac, B., Yamaguchi, H., Cox, D.
  • Journal Title: J. Cell Sci. 121 Pages: 379-390
• [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
• [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
• [Journal Article] WASP family members and Formin proteins coordinate regulation of cell protrusions in carcinoma cells (2008)
  • Author(s): Sarniento, C., Wang, W., Dovas, A., Yamaguchi, H., Sidani, M., El-Sibai, M., DesMarais, V., Holman, H. A., Kitchen, S., Backer, J. M., Alberts, A., Condeelis, J.
  • Journal Title: J. Cell Biol. 180 Pages: 1219-1232
• [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
• [Journal Article] A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis (2008)
  • Author(s): 8.Philippar, U., Roussos, E. T., Oser, M., Yamaguchi, H., Kim, H. D., Giampieri, S., Wang, Y., Goswami, S., Wyckoff, J. B., Lauffenburger, D. A., Sahai, E., Condeelis, J. S., Gertler, F. B.
  • Journal Title: Dev. Cell 15 Pages: 813-828
• [Journal Article] Dominique Simon-Chazottes, Jean-Louis Guenet, Thomas Franz, Alopecia and male infertility in oligotriche mutant mice are caused by a deletion on distal chromosome 9 (2008)
  • Author(s): Runkel1, F., Aubin, I., Bussow, H., Fukami, K., Nakamura, Y.
  • Journal Title: Mamm. Genome 19 Pages: 691-702
• [Journal Article] Phospholipase Cdl is an essential molecule downstream of Foxnl, the generesponsible for the nude mutation, in normal hair development. (2008)
  • Author(s): Nakamura Y., et al
  • Journal Title: FASEB J. 22 Pages: 841-849
  • Peer Reviewed
• [Journal Article] Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. (2008)
  • Author(s): Sakaue-Sawano A., et al.
  • Journal Title: Cell 132 Pages: 341-343
  • Peer Reviewed
• [Journal Article] Reduced fertility of mousu epididymal sperm lacking Prss21/Tesp5 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] Phospholipase Cδ1 is an essential molecule downstream of Foxnl, the gene responsible for the nude mutation, in normal hair development. (2008)
  • Author(s): Nakamura Y., et. al.
  • Journal Title: FASEB J. (in press)
  • Peer Reviewed
• [Journal Article] Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. (2008)
  • Author(s): Sakaue-Sawano A., et. al.
  • Journal Title: Cell 1322 Pages: 341-343
  • Peer Reviewed
• [Journal Article] Lack of phospholipase C-d1 induces skin inflammation. Biochem (2007)
  • Author(s): Ichinohe, M., Nakamura, Y., Sai, K., Nakahara, M., Yamaguchi, H., Fukami, K.
  • Journal Title: Biophys. Res. Comm. 356 Pages: 912-8
• [Journal Article] Phospholipase C-related inactive protein is involved in trafficking of gamma2 subunit-containing GABA(A) receptors to the cell surface (2007)
  • Author(s): Mizokami, A., Kanematsu, T., Ishibashi, H., Yamaguchi, T., Tanida, I., Takenaka, K., Nakayama, K.I., Fukami, K., Takenawa, T., Kominami, E., Moss, S. J., Yamamoto, T., Nabekura, J., Hirata, M.
  • Journal Title: J. Neurosci 27 Pages: 1692-701
• [Journal Article] Male-specific sterility caused by the loss of CR16 (2007)
  • Author(s): Suetsugu, S., Banzai, Y., Fukami, K., Kataoka, Y., Takai, Y., Yoshida, N., Takenawa, T.
  • Journal Title: Genes Cells 12 Pages: 721-33
• [Journal Article] PIASy controls ubiquitination-dependent proteasomal degradation of Ets-1 (2007)
  • Author(s): Nishida, T., Terashima, M., Fukami, K., Yamada, Y.
  • Journal Title: Biochem J. 405 Pages: 481-8
• [Journal Article] Repression of E1AF transcriptional activity by sumoylation and PIASy (2007)
  • Author(s): Nishida, T., Terashima, M., Fukami, K., Yamada, Y.
  • Journal Title: Biochem. Biophys. Res. Comm. 360 Pages: 226-32
• [Journal Article] Polarity-regulating kinase protease-activated receptor 1/microtubule affinity-regulating kinase 2 negatively regulates development of dendrites on hippocampal neurons (2007)
  • Author(s): Terabayashi, T., Itoh, T. J., Yamaguchi, H., Yoshimura, Y., Funato, Y., Ohno, S., Miki, H.
  • Journal Title: J. Neurosci 27 27 Pages: 13098-13107
• [Journal Article] Proteolytic processing of phospholipase Cζ and [Ca^<2+>]i oscillations during mammalian fertilization (2007)
  • Author(s): Kurokawa, M, Yoon, S. Y., Alfandari, D., Fukami, K., Sato, K., Fissore, R. A.
  • Journal Title: Dev. Biol. 312 Pages: 407-18
• [Journal Article] Expression and characterization of a pleckstrin homology domain in phospholipase C (2007)
  • Author(s): Imai, T., Kasai, K., Kurita, J., Fukami, K., Tashiro, M., Shimotakahara, S.
  • Journal Title: PLC-η1.Protein Expr. Purif 56 Pages: 247-52
• [Journal Article] Lack of phospholipase C-δ1 induces skin inflammation (2007)
  • Author(s): Ichinohe M., et. al.
  • Journal Title: Biochem. Biophys. Res. Comm. 356 Pages: 912-8
  • Peer Reviewed
• [Journal Article] N-WASP and cortactin are involved in invadopodium-dependent chemotaxis to EGF in breast tumor cells
  • Author(s): DesMarais, V., Yamaguchi, H., Oser, M., Soon, L., Mouneimne, G., Sarmiento, C., Eddy, R., Condeelis, J.
  • Journal Title: Cell Motil. Cytoskeleton (in press)
• [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] Protein domains of cortactin have diverse functions in the stages of invadopodium assembly and maturation (2008)
  • Author(s): Oser, M., Yamaguchi, H., Arias, M., Eddy, R., DesMarais, V., Van Rheenen, J., Condeelis, J.
  • Organizer: 48^<th> The American Society for Cell Biology Annual Meeting
  • Place of Presentation: San Francisco, USA
• [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(シンポジウムオーガナイザー、招待講演)
• [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(シンポジウム、招待講演)
  • 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] 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] C3H10T1/2間葉系幹細胞の脂肪細胞分化における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] MyosinVI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第31回日本分子生物学会年
  • 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31回日本分子生物学会年会・第81回日本
  • 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] 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(ワークショップオーガナイザー、招待講演)
  • Place of Presentation: 横浜
• [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: 33^<rd> FEBS Congress & 11^<th>IUBMB Conference
  • Place of Presentation: Athens, Greece
• [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] 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 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] 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大会
  • 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] 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] Phospholipase C delta-type isozymes have individual physiological functions in mice (2008)
  • Author(s): Fukami, K., Nakamura, Y.
  • Organizer: Pohang Conference on Cellular Signaling
  • Place of Presentation: Pohang, Korea(招待講演)
• [Presentation] Physiological roles of Phospholipase Cδ1 in regulation of epidermal homeostasis and formation of hair follicle. (2007)
  • Author(s): Fukami K., et. al.
  • Organizer: 48th International symposium on regulation activity and synthesis in normal and neoplastic tissues
  • Place of Presentation: Bologna, Italy
  • Year and Date: 2007-09-25
• [Presentation] 毛形成におけるホスホリパーゼ Cd1の生理機能の解析 (2007)
  • Author(s): 平田真之、中村由和、深見希代子
  • Organizer: 第49回日本脂質生化学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-06-06
• [Presentation] Use of Biosensors to track the initiation of cell motility in tumor cells in vitro and in vivo (2007)
  • Author(s): Van Rheenen, J., Oser, M., Kedrin, D., Wyckoff, J., Yamaguchi, H., van Roosmalen, W., Segall, J., and Condeelis, J.
  • Organizer: 47th The American Society for Cell Biology Annual Meeting
  • Place of Presentation: Washington DC, USA
• [Presentation] Protein domains of cortactin have diverse roles in the formation, dynamics, and matrix degradation of invadopodia (2007)
  • Author(s): Oser, M., Yamaguchi, H., Van Rheenen, J., Cortesio, C., Hottenlocher, A., and Condeelis, J.
  • Organizer: 47th The American Society for Cell Biology Annual Meeting
  • Place of Presentation: Washington DC, USA
• [Presentation] 神経細胞特異的に発現するホスホリパーゼC(PLC)η2の結合タンパク質の解析 (2007)
  • Author(s): 橋口祥子, 中原真道、永田静香、山口英樹、深見希代子
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
• [Presentation] ホスホリパーゼC(PLC)d3の神経突起伸長への関与 (2007)
  • Author(s): 五十嵐隆公、中村由和、河内全、山口英樹、深見希代子
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
• [Presentation] Phospholipase Cd3はmyosin IVと結合し内耳有毛細胞において共発現する (2007)
  • 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30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
• [Presentation] Physiological roles of Phospholipase Cδ1 in regulation of epidermal homeostasis and formation of hair follicle (2007)
  • Author(s): Fukami, K., Ichinohe M., Matsuura, H., Nakamura, Y.
  • Organizer: 48^<th> International symposium on regulation activity and synthesis in normal and neoplastic tissues
  • Place of Presentation: Bologna, Italy(招待講演)
• [Presentation] ホスフォリパーゼCシグナリングと病態 (2007)
  • Author(s): 深見希代子
  • Organizer: 第69回バイオサイエンス研究会
  • Place of Presentation: 神戸(招待講演)
• [Presentation] Molecular mechanisms of invadopodium formation : the roles of phosphoinositides and lipid microdomains (2007)
  • Author(s): Yamaguchi, H., Fukami, K.
  • Organizer: 5^<th> Korea-Japan Conference on Cellular Signaling for Young Scientists
  • Place of Presentation: Gyeongju, South Korea
• [Presentation] Lack of phospholipase C-d1 induces skin inflammation (2007)
  • Author(s): Ichinohe, M., Hirata, M., Takenawa, T., Nakamura, Y.,Fukami, K.
  • Organizer: The 5^<th> Japan-Korea Conference on Cellular Signaling for Young Scientists
  • Place of Presentation: Gyeongju, Korea
• [Presentation] Functional analysis of Phospholipase Cd1 in normal coat development (2007)
  • Author(s): Hirata, M., Ichinohe, M., Matsuura, H., Nakamura, Y, Fukami, K.
  • Organizer: The 5^<th> Japan-Korea Conference on Cellular Signaling for Young Scientists
  • Place of Presentation: Gyeongju, Korea
• [Presentation] 神経細胞におけるホスフォリパーゼCh2の生理機能の解析 (2007)
  • Author(s): 中原真道、橋口祥子、永田静香、山口英樹、深見希代子
  • Organizer: 第49回日本脂質生化学会
  • Place of Presentation: 札幌
• [Presentation] PLCd1の欠損は皮膚炎症を惹起する (2007)
  • Author(s): 一戸学、中村由和、深見希代子
  • Organizer: 第49回日本脂質生化学会
  • Place of Presentation: 札幌
• [Presentation] 皮膚炎症の惹起におけるホスホリパーゼC-d1の役割 (2007)
  • Author(s): 一戸学、中村由和、佐井賢太郎、深見希代子
  • Organizer: 第77回東京医科大学・東京薬科大学・免疫アレルギー研究会
  • Place of Presentation: 東京
• [Presentation] 浸潤突起形成の分子機構と癌浸潤転移における役割 (2007)
  • Author(s): 山口英樹、深見希代子
  • Organizer: 第40回日本発生生物学会第59回日本細胞生物学会合同大会(ミニシンポジウム、招待講演)
  • Place of Presentation: 福岡
• [Book] Physiological functions of Phospholipase C delta-type. (2008)
  • Author(s): Fukami, K., Ichinohe, M., Hirata, M., Nakamura, Y.
  • Publisher: Advan. Enzyme Regul(48)
• [Book] Multiple roles of phosphoinositide-specific phospholipase C isozymes (2008)
  • Author(s): Suh, P. G., Park, J. I., Manzoli, L., Cocco, L., Peak, J. C., Katan, M., Fukami, K., Kataoka, T., Yun, S.,and Ryu, S. H.
  • Publisher: BMB Rep. 41
• [Book] BMB Rep (2008)
  • Author(s): Suh P. G., et al.
  • Publisher: Multiple roles of phosphoinositide-specific phospholipase C isozymes.
• [Book] Advan. Enzyme Regul.
  • Author(s): Fukami K., et. al.
  • Publisher: ELSEVIER(in press)