Spatiotemporal activation of Rac1 for engulfment of apoptotic cells
Spatiotemporal activation of Rac1 for engulfment of apoptotic cells
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DOI：
10.1073/pnas.0803677105
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发表时间：
2008-07-08
影响因子：
11.1
通讯作者：
Nagata, Shigekazu
中科院分区：
文献类型：
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作者：
Nakaya, Michio;Kitano, Masahiro;Nagata, Shigekazu
凋亡细胞的吞噬需要吞噬细胞协同激活调节肌动蛋白动力学的Rho家族GTP酶。在这里，我们使用FRET生物传感器来可视化凋亡细胞吞噬过程中Rac 1的时空激活。我们报道凋亡细胞通常被吞噬细胞的片状伪足吞噬，在那里Rac 1被激活。通常，凋亡细胞在相同的片状伪足部位被相继吞噬，表明凋亡细胞存在门户。在这个位置，激活的Rac 1被募集形成由肌动蛋白斑块组成的吞噬杯。当吞噬杯关闭时，Rac 1下调，肌动蛋白斑块突然分解。组成型活性Rac 1在吞噬杯中停留的时间比野生型Rac 1更长，并且在表达组成型活性形式Rac 1的细胞中，吞噬杯的关闭显着延迟，导致吞噬效率低下。这些结果表明，激活的Rac 1是必要的组装F-肌动蛋白，但关闭吞噬杯需要Rac 1被灭活。
The engulfment of apoptotic cells requires phagocytes to coordinately activate Rho family GTPases that regulate actin dynamics. Here, we used a FRET biosensor to visualize the spatiotemporal activation of Rac1 during engulfment of apoptotic cells. We report that apoptotic cells were usually engulfed by the phagocytes' lamellipodia, where Rac1 was activated. Often, apoptotic cells were engulfed successively at the same lamellipodial site, suggesting the presence of portals for apoptotic cells. At this location, the activated Rac1 was recruited to form phagocytic cups that were comprised of actin patches. When the phagocytic cup was closed, Rac1 was down-regulated, and the actin patches were abruptly broken down. The constitutively active Rac1 remained at phagocytic cup for a longer period than the wild-type Rac1, and the closure of the phagocytic cup was significantly delayed in cells expressing a constitutive active form of Rac1, resulting in inefficient engulfment. These results indicate that activated Rac1 is necessary to assemble F-actin, but closing the phagocytic cup requires Rac1 to be deactivated.