| Project/Area Number |
18K06834
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 48010:Anatomy-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
Wakayama Tomohiko 熊本大学, 大学院生命科学研究部(医), 教授 (70305100)
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| Co-Investigator(Kenkyū-buntansha) |
玉井 郁巳 金沢大学, 薬学系, 教授 (20155237)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 精子形成 / 細胞接着分子 / ミトコンドリア / 鞭毛形成 / 免疫沈降 / 質量分析 / 細胞小器官 / 形態形成 / 細胞小器官の配置 |
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| Outline of Final Research Achievements |
The nucleus and organelles are arranged in designated position. In sperm, the nucleus localizes at the head, centrosome does at the neck and mitochondria and flagella do at the tail. Cell adhesion molecules 1 (CADM1) is localized in the posterior portion of elongating spermatids. Knockout (KO) mice for CADM1 develop male infertility due to defective spermatogenesis showing disordered mitochondrial position and abnormal formation of flagella. It is unknown to regulate the mitochondrial localization and flagellar formation by CADM1. We examined which molecules interact with CADM1, its adaptor molecule BSPRY, Iba-1 MPP6 and sperm flagellar protein SEPTEX-1. Only Mrap and Tex22 could interact with CADM1, BSPRY, MPP6, Iba-1, SEPTEX-1. However, knockout mice for Mrap and Tex22 showed no infertility. These findings suggest that CADM1 is indispensable for normal positioning of mitochondria and flagellar formation.
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| Academic Significance and Societal Importance of the Research Achievements |
精子形成では、造精幹細胞を含む精祖細胞が増殖・分化をして次世代に遺伝情報を伝える精子が形成される。精子は、頭部に先体や核があり、ミトコンドリアを有する鞭毛を尾部にもつ高度に分化した細胞である。細胞接着分子CADM1のノックアウトマウスでは、ミトコンドリアの配置異常を伴う鞭毛形成異常を生じた。このミトコンドリア配置と鞭毛形成を制御するCADM1が相互作用する分子が明らかになり、本研究の成果は、男性不妊症の原因解明に寄与する。
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