| Project/Area Number |
16K08238
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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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| Research Field |
Biological pharmacy
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| Research Institution | Nagasaki University |
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Principal Investigator |
TANIMURA Susumu 長崎大学, 医歯薬学総合研究科(薬学系), 准教授 (90343342)
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| Co-Investigator(Kenkyū-buntansha) |
武田 弘資 長崎大学, 医歯薬学総合研究科(薬学系), 教授 (10313230)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 細胞運動 / ミオシン / リン酸化 / エンドサイトーシス / シグナル伝達 / カベオラ / 癌 |
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| Outline of Final Research Achievements |
Dysregulation of cell motility response leads to cancer metastasis. We have previously shown that Myosin1E-SH3P2 complex regulates cell motility, however the molecular mechanisms of which still remains unknown. Here, we show that Myosin1E binds to SH3 domain of Sorting nexin9 (SNX9) through its proline-rich region within TH2 domain and to Cavin3-Caveolin1 complex through its SH3 domain. Myosin1E co-localizes with SNX9 and F-actin at the leading edge of migrating cells. siRNA-mediated knockdown of Myosin1E, SNX9, or Cavin3 inhibits cell motility. Overexpression of SH3P2 using doxycycline-inducible TetON system suppressed localization of Myosin1E to plasma membrane as well as cell motility. These results suggest that Myosin1E released from SH3P2 promotes cell motility via the interaction with SNX9 and Cavin3-Caveolin1 complex at plasma membrane.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞運動制御メカニズムの破綻はがん細胞の浸潤転移につながるが、その分子メカニズムについては依然として不明な点が多い。本研究によって、Myosin1Eタンパク質複合体を切り口とした新たな細胞運動制御の分子メカニズムが明らかとなった。本研究成果より、細胞運動制御メカニズムの一端が明らかになったことに加え、がんの浸潤転移を抑制する上で有効な標的分子の同定につながる可能性が予想され、がん転移抑制剤開発に新しい展開をもたらすことなどが期待される。
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