2010 Fiscal Year Final Research Report
Identification of multiple functions of semaphorin-signals
| Project/Area Number |
20390142
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Osaka University |
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Principal Investigator |
KUMANOGOH Atsushi Osaka University, 微生物病研究所, 教授 (10294125)
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| Project Period (FY) |
2008 – 2010
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| Keywords | セマフォリン / EARP2 / 破骨細胞 |
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| Research Abstract |
Podosomes are recently rediscovered highly dynamic actin-rich structural and functional modules that form close contact with the surrounding substrate. They play a role in the control of migration, tissue invasion, and matrix remodeling of highly motile cells, including lymphocytes, macrophages, dendritic cells, and osteoclasts. In osteoclasts, the compaction of podosomes induces the formation of a tight adhesive contact, the sealing zone, which defines a subosteoclastic environment specialized for bone resorption. Integrins and the Rho family small GTPases are key regulators of podosome rearrangements. However, it remains to be determined how the activation of integrins and Rho family GTPases is regulated during osteoclast podosome rearrangements. Here, we demonstrate a crucial role for the FERM domain-containing guanine nucleotide exchange factor (GEF), FARP2, in osteoclast podosome rearrangements and resorbing activity. We determine by live cell imaging and biochemical assays that FARP2 is required for localized activation of GTP-bound Rac1 into podosome-ring like structures. In addition, FARP2 is relevant to integrin β3 activity during osteoclastogenesis. Furthermore, FARP2 deficiency results in reduced formation of multinucleated osteoclasts and resorption pits compared to wild-type osteoclasts (controls). Collectively, our findings reveal an integral role of FARP2 for regulation of Racl and integrin β3 throughout podosome rearrangement in osteoclastogenesis.
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[Journal Article] Structural basis for semaphorin signalling through the plexin receptor.2010
Author(s)
Nogi T, Yasui N, Mihara E, Matsunaga Y, Noda M, Yamashita N, Toyofuku T, Uchiyama S, Goshima Y, Kumanogoh A, Takagi J.
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Journal Title
Nature 467
Pages: 1123-1127
Peer Reviewed
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[Journal Article] Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II.2010
Author(s)
Takamatsu H, Takegahara N, Nakagawa Y, Tomura M, Taniguchi M, Friedel RH, Rayburn H, Tessier-Lavigne M, Yoshida Y, Okuno T, Mizui M, Kang S, Nojima S, Tsujimura T, Nakatsuji Y, Katayama I, Toyofuku T, Kikutani H, Kumanogoh A.
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Journal Title
Nat Immunol. 11
Pages: 594-600
Peer Reviewed
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