Signaltransduction of cytoskeleton and cell movement

细胞骨架和细胞运动的信号转导

• 批准号: 12219202
• 负责人: TAKENAWA Tadaomi
• 金额: $ 142.59万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12219202/
• 关键词: Actin cytoskeleton; Invasion; Metastasis; WAVE; B16 cells; lamellipodia; 癌細胞; 細胞運動; アクチン; WASP; 糸状突起; 葉状突起; 系状突起

We found N-WASP and WAVE which are involved in actin polymerization at leading edge, and induce filopodia and lamellipodia formation. There are 3 types of WAVE. Among them, WAVE2 is ubiquitously expressed in a wide of tissues and plays crucial role in cell movement at leading edge.We next prepared WAVE1 and 2 knock out mice and established mouse embryonic fibroblasts which do not have WAVE1 or WAVE2. WAVE2-deficient MEF did not induce lamellipodia formation in response to chemoatractants, and speed of cell movement was very slow. On the other hand, WAVE1-deficient MEFdidnot induce dorsal ruffles, though lamellipodia formation was still observed.We also examined whether WAVE is involved in invasion of B16/F10 cells that are high metastatic cell lines. WAVE1 knock down did not affect the cell movement in 3 D collagen. In contrast, WAVE2 knock down inhibited cell movement, invasion in collagen gels. B16/F10 cells of WAVE2 knock down was also suppressed in metastasis to lung.

我们发现N-WASP和WAVE参与肌动蛋白的前缘聚合，诱导丝状足和板足的形成。WAVE有三种类型。其中，WAVE2在多种组织中普遍表达，在细胞前沿运动中起着至关重要的作用。接下来，我们制备了WAVE1和2敲除小鼠，并建立了不含WAVE1和WAVE2的小鼠胚胎成纤维细胞。在趋化剂作用下，缺乏wave2的MEF不诱导板状足形成，细胞运动速度非常缓慢。另一方面，wave1缺失的mef1不诱导背褶，但仍观察到板足形成。我们还研究了WAVE是否参与高转移细胞系B16/F10细胞的侵袭。WAVE1敲低不影响三维胶原的细胞运动。相反，WAVE2敲低抑制了胶原蛋白凝胶中的细胞运动和入侵。WAVE2敲低的B16/F10细胞在肺转移中也受到抑制。

项目成果

Yamaguchi,H.: "Two tandem verprolin homology domains are necessary for a strong activation of Arp2/3 complex-induced actin polvmerization and induction of microspike formation by N-WASP"Proc.Natl.Acad.Sci.USA.. 97. 12631-12636 (2000)

Yamaguchi,H.：“两个串联的维普林同源结构域对于 Arp2/3 复合物诱导的肌动蛋白聚合和 N-WASP 诱导微刺形成的强烈激活是必需的”Proc.Natl.Acad.Sci.USA.. 97. 12631

WAVE2, involved in directed cell migration, is required for cardiovascular development.

WAVE2 参与定向细胞迁移，是心血管发育所必需的。

• 发表时间: 2003
• 期刊: Nature 424
• 作者: Yamazaki;D.;Suetsugu;S.;Miki;H.;Kataoka;Y.;Nishikawa;S.;Fujiwara;T.;Yoshida;N.;Takenawa;T.
• 通讯作者: T.

WICH, a member of WASP-interacting protein family, cross-links actin filaments.

WICH 是 WASP 相互作用蛋白家族的成员，可交联肌动蛋白丝。

• 发表时间: 2005
• 期刊: Biochem.Biophys.Res Commun. 328・4
• 作者: Kato M;Takenawa T.
• 通讯作者: Takenawa T.

Suetsugu, S., Hattori, M., Miki, H., Tezuka, T., Yamamoto, T., Mikoshiba, K., Takenawa, T.: "Sustained Activation of N-WASP through Phosphorylation Is Essential for Neurite Extension"Dev Cell. 3. 645-658 (2002)

Suetsugu, S.、Hattori, M.、Miki, H.、Tezuka, T.、Yamamoto, T.、Mikoshiba, K.、Takenawa, T.：“通过磷酸化持续激活 N-WASP 对于神经突延伸至关重要”

Phospholipase C delta-type consists of three isozymes : bovine PLCdelta2 is a homologue of human/mouse PLCdelta4.

磷脂酶 C δ 型由三种同工酶组成：牛 PLCdelta2 是人/小鼠 PLCdelta4 的同源物。

• 发表时间: 2004
• 期刊: Biochem.Biophys.Res.Commun. 23
• 作者: Irino;Y.;Cho;H.;Nakamura;Y.;Nakahara;M.;Furutani;M.;Suh;P.G.;Takenawa;T.;Fukami;K.
• 通讯作者: K.