Analysis of phosphorylation signals in mammalian meiotic checkpoints

• Project/Area Number: 24590263
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Gunma University
• Principal Investigator: KOGO Hiroshi 群馬大学, 医学(系)研究科(研究院), 講師 (20282387)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 減数分裂 / チェックポイント / リン酸化 / 対合不全 / 転写抑制 / 不妊 / ノックアウトマウス / 性染色体 / 習慣流産

Outline of Final Research Achievements

In the present study, we analyzed the phosphorylation of HORMAD1 and HORMAD2, which are recently identified as key molecules for mammalian meiotic checkpoints. We generated phospho-specific antibodies against multiple phosphorylation sites of HORMAD1 and HORMAD2, and examined their distribution in mouse spermatocytes and oocytes by immunofluorescence staining. As a result, we found that HORMAD1 was phosphorylated at Ser307 along entire unsynapsed axes without any DNA double strand breaks. We also found that HORMAD2 phosphorylation at Ser284 was localized on the particular unsynapsed axes where pseudo sex bodies were formed, while HORMAD2 distributes along entire unsynapsed axes, suggesting that HORMAD2 phosphorylation at Ser284 might be involved in the activation process of synapsis checkpoint. These results provide clues to reveal the molecular mechanism of meiotic checkpoint signaling in mammals.

Research Products

• [Journal Article] Requirement of DLG1 for cardiovascular development and tissue elongation 1 during cochlear, enteric, and skeletal development: possible role in convergent extension. (2015)
  • Author(s): Akiko Iizuka-Kogo, Takao Senda, Tetsu Akiyama, Atsushi Shimomura, Ryuji Nomura, Yoshimi Hasegawa, Ken-ichi Yamamura, Hiroshi Kogo, Nobuhiko Sawai, Toshiyuki Matsuzaki
  • Journal Title: PLoS ONE Volume: 10 Issue: 4 Pages: e0123965-e0123965
  • DOI: 10.1371/journal.pone.0123965
  • Peer Reviewed / Open Access
• [Journal Article] Fatty acid-binding protein 7 regulates function of caveolae in astrocytes through expression of caveolin-1. (2015)
  • Author(s): Yoshiteru Kagawa, Yuki Yasumoto, Kazem Sharifi, Majid Ebrahimi, Ariful Islam, Hirofumi Miyazaki, Yui Yamamoto, Tomoo Sawada, Hiroko Kishi, Sei Kobayashi, Motoko Maekawa, Takeo Yoshikawa, Eiichi Takaki, Akira Nakai, Hiroshi Kogo, Toyoshi Fujimoto and Yuji Owada
  • Journal Title: Glia Volume: 63 Issue: 5 Pages: 780-794
  • DOI: 10.1002/glia.22784
  • Peer Reviewed / Open Access
• [Journal Article] Age-related decrease of meiotic cohesins in human oocyte (2014)
  • Author(s): Tsutsumi M, Fujiwara R, Nishizawa H, Ito M, Kogo H, Inagaki H, Ohye T, Kato T, Fujii T, Kurahashi H
  • Journal Title: PLoS One Volume: 9, Issue: 5 Pages: 1-8
  • DOI: 10.1371/journal.pone.0096710
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of Repeated Administration of Pilocarpine and Isoproterenol on Aquaporin-5 Expression in Rat Salivary Glands (2013)
  • Author(s): Susa T, Sawai N, Aoki T, Iizuka-Kogo A, Kogo H, Negishi A, Yokoo S, Takata K, Matsuzaki T
  • Journal Title: ACTA HISTOCHEMICA ET CYTOCHEMICA Volume: 46 Issue: 6 Pages: 187-197
  • DOI: 10.1267/ahc.13037
  • NAID: 130003381873
  • ISSN: 0044-5991, 1347-5800
  • Peer Reviewed
• [Journal Article] Two sequential cleavage reactions on cruciform DNA structures cause palindrome-mediated chromosomal translocations (2013)
  • Author(s): Inagaki H, Ohye T, Kogo H, Tsutsumi M, Kato T, Tong M, Emanuel BS, Kurahashi H
  • Journal Title: Nat Commun Volume: 4 Issue: 1 Pages: 1592-1592
  • DOI: 10.1038/ncomms2595
  • Peer Reviewed
• [Journal Article] HORMAD2 is essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity (2012)
  • Author(s): Kogo H, Tsutsumi M, Ohye T, Inagaki H, Kiyonari H, Kurahashi H
  • Journal Title: Genes Cells Volume: 17 Issue: 11 Pages: 897-912
  • DOI: 10.1111/gtc.12005
  • Peer Reviewed
• [Journal Article] HORMAD1-dependent checkpoint/surveillance mechanism eliminates asynaptic oocytes (2012)
  • Author(s): Kogo, H., Tsutsumi, M., Ohye, T., Inagaki, H., Abe, T., Kurahashi, H.
  • Journal Title: Genes Cells Volume: 17 Issue: 6 Pages: 439-454
  • DOI: 10.1111/j.1365-2443.2012.01600.x
  • Peer Reviewed
• [Journal Article] Screening of genes involved in chromosome segregation during meiosis I: in vitro gene transfer to mouse fetal oocytes. (2012)
  • Author(s): Tsutsumi M, Kowa-Sugiyama H, Bolor H, Kogo H, Inagaki H, Ohye T, Yamada K, Taniguchi-Ikeda M, Toda T, Kurahashi H.
  • Journal Title: J Hum Genet Volume: 57 Issue: 8 Pages: 515-522
  • DOI: 10.1038/jhg.2012.61
  • NAID: 10031056588
  • Peer Reviewed
• [Journal Article] Molecular basis of maternal age-related increase in oocyte aneuploidy (2012)
  • Author(s): Kurahashi H, Tsutsumi M, Nishiyama S, Kogo H, Inagaki H, Ohye T
  • Journal Title: Congenit Anom (Kyoto) Volume: 52 Issue: 1 Pages: 8-15
  • DOI: 10.1111/j.1741-4520.2011.00350.x
  • Peer Reviewed
• [Presentation] 対合チェックポイントによるマウス卵母細胞の細胞死のタイミング (2015)
  • Author(s): 向後 寛、青木 友紀、向後 晶子、澤井 信彦、松崎 利行
  • Organizer: 第120回日本解剖学会総会・全国学術集会、第92回日本生理学会大会 合同大会
  • Place of Presentation: 神戸国際会議場・展示場（兵庫県神戸市）
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 対合不全により誘導されるマウスHORMAD1の主要なリン酸化部位の同定 (2015)
  • Author(s): 菊池 悠佳、向後 寛、向後 晶子、澤井 信彦、松崎 利行
  • Organizer: 第120回日本解剖学会総会・全国学術集会、第92回日本生理学会大会 合同大会
  • Place of Presentation: 神戸国際会議場・展示場（兵庫県神戸市）
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] DNA損傷に依存しないマウスHORMAD1のリン酸化部位の同定 (2014)
  • Author(s): 向後 寛、菊池 悠佳、向後 晶子、澤井 信彦、倉橋 浩樹、松崎 利行
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] HORMAD1のハプロ不全による卵母細胞の減少とそのメカニズムの解析 (2014)
  • Author(s): 向後 寛、向後 晶子、倉橋 浩樹、松崎 利行
  • Organizer: 第119回日本解剖学会全国学術集会
  • Place of Presentation: 栃木県下野市
• [Presentation] 卵母細胞のmeiotic silencing of unsynapsed chromatin に必要なマウスHORMAD2のリン酸化 (2013)
  • Author(s): 向後 寛、堤 真紀子、向後 晶子、倉橋 浩樹、松崎 利行
  • Organizer: 第３６回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] HORMAD2 phosphorylation may be involved in the initiation of meiotic silencing of unsynapsed chromatin. (2013)
  • Author(s): Kogo H, Tsutsumi M, Iizuka-Kogo A, Kurahashi H, Matsuzaki T
  • Organizer: EMBO conference on meiosis 2013
  • Place of Presentation: ドレスデン、ドイツ
• [Presentation] 哺乳類の減数分裂における対合不全チェック機構とHORMAD2のリン酸化 (2013)
  • Author(s): 向後 寛、倉橋 浩樹、松崎 利行
  • Organizer: 第１１８回日本解剖学会全国学術集会
  • Place of Presentation: 高松
• [Presentation] 哺乳類の減数分裂における対合チェックポイントとHORMAD2のリン酸化 (2012)
  • Author(s): 向後 寛、堤 真紀子、稲垣 秀人、大江 瑞恵、倉橋 浩樹
  • Organizer: 第３５回日本分子生物学会年会
  • Place of Presentation: 博多
• [Remarks] 研究室HP
  • URL: http://anatcb.dept.med.gunma-u.ac.jp
• [Remarks] 研究室HP
  • URL: http://anatcb.dept.med.gunma-u.ac.jp
• [Remarks] Publication List
  • URL: http://anatcb.dept.med.gunma-u.ac.jp/~anat1his/pub.html