Optimization of WAVE2 complex-induced actin polymerization by membrane-bound IRSp53, PIP(3), and Rac.
Optimization of WAVE2 complex-induced actin polymerization by membrane-bound IRSp53, PIP(3), and Rac.
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DOI：
10.1083/jcb.200509067
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发表时间：
2006-05-22
期刊：
影响因子：
--
通讯作者：
Takenawa T
中科院分区：
文献类型：
--
作者：
Suetsugu S;Kurisu S;Oikawa T;Yamazaki D;Oda A;Takenawa T
WAVE2激活RAC诱导的肌动蛋白聚合的肌动蛋白相关蛋白(Arp)2/3复合体，并与Sra1/PIR121、NAP1、ABI1和HSPC300形成一个大的WAVE2蛋白质复合体。IRSP53可与RAC和CDC42结合，并建议将RAC连接到WAVE2。我们发现，通过RNA干扰敲除IRSp53减少了片状磷脂的形成，而不减少WAVE2复合体的数量。在IRSp53基因敲除细胞中，WAVE2定位于细胞边缘。此外，激活的CDC42而不是RAC减弱了WAVE2和IRSP53之间的联系。当我们在体外检测Arp2/3激活时，从细胞膜部分分离的WAVE2复合体以IRSp53依赖的方式完全激活，而从胞浆分离的WAVE2则不是。纯化的WAVE2和纯化的WAVE2复合体通过含有PIP3的脂质体被IRSP53以RAC依赖的方式激活。因此，IRSP53在活化的RAC和PIP3存在下优化WAVE2复合体的活性。
WAVE2 activates the actin-related protein (Arp) 2/3 complex for Rac-induced actin polymerization during lamellipodium formation and exists as a large WAVE2 protein complex with Sra1/PIR121, Nap1, Abi1, and HSPC300. IRSp53 binds to both Rac and Cdc42 and is proposed to link Rac to WAVE2. We found that the knockdown of IRSp53 by RNA interference decreased lamellipodium formation without a decrease in the amount of WAVE2 complex. Localization of WAVE2 at the cell periphery was retained in IRSp53 knockdown cells. Moreover, activated Cdc42 but not Rac weakened the association between WAVE2 and IRSp53. When we measured Arp2/3 activation in vitro, the WAVE2 complex isolated from the membrane fraction of cells was fully active in an IRSp53-dependent manner but WAVE2 isolated from the cytosol was not. Purified WAVE2 and purified WAVE2 complex were activated by IRSp53 in a Rac-dependent manner with PIP3-containing liposomes. Therefore, IRSp53 optimizes the activity of the WAVE2 complex in the presence of activated Rac and PIP3.
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影响因子：
46.9
作者：
Nagai, T;Ibata, K;Miyawaki, A
通讯作者：
Miyawaki, A
DOI：
10.1083/jcb.152.3.579
发表时间：
2001-02-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Govind S;Kozma R;Monfries C;Lim L;Ahmed S
通讯作者：
Ahmed S
影响因子：
64.8
作者：
Miki, H;Yamaguchi, H;Takenawa, T
通讯作者：
Takenawa, T
DOI：
10.1073/pnas.0400628101
发表时间：
2004-03-30
影响因子：
11.1
作者：
Gautreau, A;Ho, HYH;Kirschner, MW
通讯作者：
Kirschner, MW
影响因子：
11.8
作者：
Suetsugu, S;Yamazaki, D;Takenawa, T
通讯作者：
Takenawa, T