| Project/Area Number |
26461108
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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 |
Cardiovascular medicine
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
朝野 仁裕 大阪大学, 医学系研究科, 講師 (60527670)
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| Co-Investigator(Renkei-kenkyūsha) |
SHINTANI Yasunori 大阪大学, 大学院医学系研究科, 助教 (20712243)
HIGO Shuichiro (KATO Hisakazu) 大阪大学, 大学院医学系研究科, 助教 (00604034)
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| Research Collaborator |
Yan Yi 大阪大学, 大学院医学系研究科, 大学院生
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | AMPK / PDLIM5 / cell migration / ＡＭＰＫ / ｃｅｌｌ ｍｉｇｒａｔｉｏｎ / AMPキナーゼ / Pdlim5 / 細胞遊走 |
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| Outline of Final Research Achievements |
We identified Pdlim5 as a novel AMPK substrate. AMPK phosphorylates Pdlim5 at Ser177. To investigate the role of Ser177 phosphorylation by AMPK, we produced the knockdown-and-rescue (KDR) system of vSMCs, in which endogenous Pdlim5 were replaced by exogenous EGFP-tagged-Pdlim5s. KDR/S177D-Pdlim5 cells exhibited perturbed cell migration compared with KDR/wild-type- and KDR/S177A-Pdlim5 cells even in the absence of AMPK activator. Furthermore, KDR/S177D-Pdlim5 cells exhibited defective lamellipodia formation. Consistent with this, KDR/S177D-Pdlim5 cells exhibited dislocation of Arp2/3 complex from the leading edge to cytosol and suppressed Rac1 activity. Finally, KDR/S177D-Pdlim5 cells disrupted the physical association with Arhgeg6, a guanine nucleotide exchange factor for Rac1. In conclusion, enhanced AMPK activation inhibits cell migration by interfering lamellipodia formation by suppressing the Arhgef6-Rac1-Arp2/3 signaling pathway via phosphorylating Pdlim5.
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