Regulation of the function of adhesion molecule SgIGSF/TSLC1 by shedding and splicing

• Project/Area Number: 19590391
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: The University of Tokyo (2008); Kobe University (2007)
• Principal Investigator: ITO Akihiko The University of Tokyo, 医科学研究所, 准教授 (80273647)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 病理学 / 発生・分化 / 脳・神経 / 免疫グロブリンスーパーファミリー / マスト細胞接着分子 / 肺癌抑制因子 / シナプス誘導接着分子 / Nectin-like molecule-2 / Shedding / スプライシング / 神経ガイダンス

Research Abstract

SgIGSF(spermatogenic immunoglobulin superfamily)/TSLC1(tumor suppressor in lung cancer-1)は、免疫グロブリン・スーパーファミリーに属する細胞膜1回貫通型の接着分子で、様々な細胞に発現しており、精子形成やシナプス形成など種々の機能を有するが、本分子の機能制御の仕組みについてはよくわかっていない。本研究課題では、SgIGSF/TSLC1の発現制御機構として転写調節(splicingによる分泌型分子の産生)と転写後調節(sheddingによる細胞外ドメイン断片の産生)が存在することを明らかにした。加えて、分泌型分子は細胞外に放出された後、神経突起上に発現する膜貫通型分子とtrans-ホモフィリックに結合することにより、神経突起の伸長方向の制御に関わることがわかった。

Research Products

• [Journal Article] Expression of a soluble isoform of cell adhesion molecule 1 in the brain and its involvement in directional neurite Outgrowth (2009)
  • Author(s): Hagiyama M, Ichiyanagi N, Kimura KB, Murakami Y, Ito A
  • Journal Title: Am J Pathol 174 Pages: 2278-2289
• [Journal Article] Expression of a soluble isoform of cell adhesion molecule 1 in the brain and its involvement in directional neurite Outgrowth (2009)
  • Author(s): Hagiyama M
  • Journal Title: American Journal of Pathology 174 Pages: 2278-2289
  • Peer Reviewed
• [Journal Article] Alternative lengthening of telomeres frequently occurs in mismatch repair system-deficient gastric carcinoma (2008)
  • Author(s): Omori Y, Nakayama F, Li D, Kanemitsu K, Semba S, Ito A, Yokozaki H
  • Journal Title: Cancer Sci 100 Pages: 413-418
  • NAID: 10025143119
• [Journal Article] CADM1 is a novel pancreatic-islet cell adhesion molecule that mediates nerve-islet cell interactions (2008)
  • Author(s): Koma Y, Furuno T, Hagiyama M, Hamaguchi K, Nakanishi M, Masuda M, Hirota S, Yokozaki H, Ito A
  • Journal Title: Gastroenterology 134 Pages: 1544-1554
• [Journal Article] Expression of cell adhesion molecule 1 in malignant pleural mesothelioma as a cause of efficient adhesion and growth on mesothelium (2008)
  • Author(s): Ito A, Hagiyama M, Mimura T, Matsumoto M, Wakayama T, Iseki S, Yokozaki H, Okada M
  • Journal Title: Lab Invest 88 Pages: 504-514
• [Journal Article] Meijer CJLM and Steenbergen RDM : Association of dense CADM1 promoter methylation and reduced protein expression in high-grade ICN and cervical SCC (2008)
  • Author(s): Overmeer RM, Snijders PJF, Claassen-Kramer D, Berkhof J, Helmerhorst TJM, Heideman DAM, Wilting SM, Ito A, Murakami Y
  • Journal Title: J Pathol 215 Pages: 388-397
• [Journal Article] Sail-associated epithelial to mesenchymal transition promotes esophageal squamous cell carcinoma motility and progression (2008)
  • Author(s): Usami Y, Satake S, Nakayama F, Matsumoto M, Ohnuma K, Komori T, Semba S, Ito A, Yokozaki H
  • Journal Title: J Pathol 215 Pages: 330-339
• [Journal Article] Expression Profiling of PBMC-based Diagnostic Gene Markers Isolated from Vasculitis Patients (2008)
  • Author(s): Kobayashi S, Ito A, Okuzaki D, Onda H, Yabuta N, Nagamori I, Suzuki K, Hashimoto H, Nojima H
  • Journal Title: DNA Res 15 Pages: 253-265
• [Journal Article] Human airway smooth muscle promotes human lung mast cell survival, proliferation, and constitutive activation : co-operative roles for stem cell factor, IL-6 and cell adhesion molecule-1 (2008)
  • Author(s): Hollins F, Kaur D, Yang W, Cruse G, Saunders R, Sutcliffe A, Berger P, Ito A, Brightling CE, Bradding P
  • Journal Title: J Immunol 181 Pages: 2772-2780
• [Journal Article] Nerve-mast cell and smooth muscle-mast cell interaction mediated by cell adhesion molecule-1 (2008)
  • Author(s): Ito A, Hagiyama M, Oonuma J
  • Journal Title: J Smooth Muscle Res(CADM1) 44 Pages: 83-93
• [Journal Article] CADM1 is a novel pancreatic-islet cell adhesion molecule that mediates nerve-islet cell interactions (2008)
  • Author(s): Koma Y
  • Journal Title: Gastroenterology 134 Pages: 1544-1554
  • Peer Reviewed
• [Journal Article] Expression of cell adhesion molecule 1 in malignant pleural mesothelioma as a cause of efficient adhesion and growth on mesothelium (2008)
  • Author(s): Ito A
  • Journal Title: Laboratory Investigation 88 Pages: 504-514
  • Peer Reviewed
• [Journal Article] Expression of cell adhesion molecule l in malignant pleural mesothelioma as a cause of efficient adhesion and growth on mesothelium (2008)
  • Author(s): Ito A
  • Journal Title: Laboratory Investigation (In press)
  • Peer Reviewed
• [Journal Article] CADMl is a novel pancreatic-islet cell adhesion molecule that mediates nerve-islet cell interactions (2008)
  • Author(s): Koma Y
  • Journal Title: Gastroenterology (In press)
  • Peer Reviewed
• [Journal Article] SgIGSF is a novel biliary-epithelial cell adhesion molecule mediating duct/ductule development (2007)
  • Author(s): Ito A, Nishikawa Y, Ohnuma K, Ohnuma I, Koma Y, Sato A, Enomoto K, Tsujimura T, Yokozaki H
  • Journal Title: Hepatology 45 Pages: 684-694
• [Journal Article] Novel marker D2-40, combined with calretinin, CEA and TTF-1 : An optimal set of immunodiagnostic markers for pleural mesothelioma (2007)
  • Author(s): Mimura T, Ito A, Sakuma T, Ohbayashi C, Yoshimura M, Tsubota N, Okita Y, Okada M
  • Journal Title: Cancer 109 Pages: 933-938
• [Journal Article] Involvement of the SgIGSF/Necl-2 adhesion molecule in degranulation of mesenteric mast cells (2007)
  • Author(s): Ito A, Hagiyama M, Oonuma J, Murakami Y, Yokozaki H, Takaki M
  • Journal Title: J Neuroimmunol 184 Pages: 209-213
• [Journal Article] Oleamide derivatives suppress the spontaneous metastasis by inhibiting connexin 26 (2007)
  • Author(s): Ohba Y, Kanao Y, Morita N, Fujii E, Hohrai M, Takatsuji M, Hirose H, Miura D, Watari A, Yutsudo M, Zhao H, Yabuta N, Ito A, Kita Y, Nojima H
  • Journal Title: Int J Cancer 121 Pages: 2801-2808
• [Journal Article] Heterophilic binding of the adhesion molecules poliovirus receptor and immunoglobulin superfamily 4A in the interaction between mouse spermatogenic and Sertoli cells (2007)
  • Author(s): Wakayama T, Sai Y, Ito A, Kato Y, Kurobo M, Murakami Y, Nakashima E, Tsuji A, Kitamura Y, Iseki S
  • Journal Title: Biol Reprod 76 Pages: 1081-1090
  • NAID: 120006380690
• [Journal Article] Electroacupuncture suppresses myostatin gene expression : cell proliferative reaction in mouse skeletal muscle (2007)
  • Author(s): Takaoka Y, Ohta M, Ito A, Takamatsu K, Sugano A, Funakoshi K, Takaoka N, Sato N, Yokozaki H, Arizono N, Goto S, Maeda E
  • Journal Title: Physiol Genomics 30 Pages: 101-110
• [Journal Article] Lats2 is an essential mitotic regulator required for the coordination of cell division (2007)
  • Author(s): Yabuta N, Okada N, Ito A, Hosomi T, Nishihara S, Sasayama Y, Fujimori A, Okuzaki D, Zhao H, Ikawa M, Okabe M, Nojima H
  • Journal Title: J Biol Chem 282 Pages: 19259-19271
• [Journal Article] A role for connexin 26 in metastasis of human melanoma : communication between melanoma and endothelial cells via connexin 26 (2007)
  • Author(s): Saito-Katsuragi M, Asada H, Niizeki H, Katoh F, Masuzawa M, Tsutsumi M, Kuniyasu H, Ito A, Nojima H, Miyagawa S
  • Journal Title: Cancer 110 Pages: 1162-1172
• [Journal Article] SgIGSF is a novel biliary-epithelial cell adhesion molecule mediating duct/ductule development (2007)
  • Author(s): Ito A
  • Journal Title: Hepatology 46 Pages: 684-694
  • Peer Reviewed
• [Presentation] フェムト秒レーザーによる神経-マスト細胞間接着力の測定 (2009)
  • Author(s): 伊藤彰彦
  • Organizer: 日本病理学会
  • Place of Presentation: 京都
  • Year and Date: 2009-05-03
• [Presentation] フェムト秒レーザーを用いた新規細胞間接着力測定法 (2008)
  • Author(s): 伊藤彰彦
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] フェムト秒レーザーを用いた新規細胞間接着力測定法 (2008)
  • Author(s): 伊藤彰彦
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] フェムト秒レーザーを用いた神経-マスト細胞間接着力の測定 : CADM1接着分子の関与 (2008)
  • Author(s): 伊藤彰彦
  • Organizer: 日本アレルレギー学会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-27
• [Presentation] CADM1 promotes nerve-pancreatic islet cell interaction and contributes to hormonal function of islet cell tumors (2008)
  • Author(s): 伊藤彰彦
  • Organizer: 日本癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] 膵島細胞腫瘍における接着分子CADM1の発現 : ホルモン機能性との相関 (2008)
  • Author(s): 伊藤彰彦
  • Organizer: 日本病理学会
  • Place of Presentation: 金沢
  • Year and Date: 2008-05-15
• [Presentation] Shedding of CADM1: molecular difference between a soluble isoform and theN-terminal fragment produced by shedding (2007)
  • Author(s): 大沼 潤子
  • Organizer: 第66回 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Book] CADM1 : a new mast-cell adhesion molecule that mediates interaction with fibroblasts, nerves, and smooth muscles in Mast Cells : Roles, Interactions and Disorders (eds, Jonas F. Jung and Luca T. Scholz) (2008)
  • Author(s): Ito A, Hagiyama M
  • Publisher: Nova Science Publishers
• [Book] Mast Cells : Roles, Interactions and Disorders (2008)
  • Author(s): Ito A
  • Publisher: Nova Science Publishers