Class I and class III phosphoinositide 3-kinases are required for actin polymerization that propels phagosomes.
Class I and class III phosphoinositide 3-kinases are required for actin polymerization that propels phagosomes.
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DOI：
10.1083/jcb.201004005
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发表时间：
2010-11-29
期刊：
影响因子：
--
通讯作者：
Grinstein S
中科院分区：
文献类型：
--
作者：
Bohdanowicz M;Cosío G;Backer JM;Grinstein S
通过补体受体（CR 3）的接合形成的吞噬体通过在吞噬体膜上的肌动蛋白“彗星尾”的PI 3 K驱动的形成在巨噬细胞内移动。肌动蛋白聚合驱动伪足的延伸，伪足捕获和吞噬吞噬目标。聚合的肌动蛋白随后随着吞噬空泡的封闭而解离，并从质膜上脱离。我们发现，吞噬体形成的整合素，作为补体受体（CR 3）进行肌动蛋白聚合的第二波，导致形成“彗星尾巴”，推动细胞内的空泡。肌动蛋白尾的形成伴随着并需要由I类磷酸肌醇3-激酶（PI 3 Ks）在吞噬体膜上重新形成PI（3，4）P2和PI（3，4，5）P3。尽管磷脂酰肌醇磷酸酶Inpp 5 B被募集到新生的吞噬体中，但在吞噬体密封后，它迅速从膜上脱离。Inpp 5 B的分离需要PI（3）P的形成。因此，III类PI 3 K活性也是PI（4，5）P2和PI（3，4，5）P3的积累以及肌动蛋白尾形成所必需的。这些实验揭示了导致PI（3，4）P2和PI（3，4，5）P3在内膜中形成和信号传导的新PI（3）P敏感途径。
Phagosomes formed by engagement of complement receptors (CR3) are moved within macrophages by PI3K-driven formation of actin “comet tails” on the phagosomal membrane. Actin polymerization drives the extension of pseudopods that trap and engulf phagocytic targets. The polymerized actin subsequently dissociates as the phagocytic vacuole seals and detaches from the plasma membrane. We found that phagosomes formed by engagement of integrins that serve as complement receptors (CR3) undergo secondary waves of actin polymerization, leading to the formation of “comet tails” that propel the vacuoles inside the cells. Actin tail formation was accompanied by and required de novo formation of PI(3,4)P2 and PI(3,4,5)P3 on the phagosomal membrane by class I phosphoinositide 3-kinases (PI3Ks). Although the phosphatidylinositide phosphatase Inpp5B was recruited to nascent phagosomes, it rapidly detached from the membrane after phagosomes sealed. Detachment of Inpp5B required the formation of PI(3)P. Thus, class III PI3K activity was also required for the accumulation of PI(4,5)P2 and PI(3,4,5)P3 and for actin tail formation. These experiments reveal a new PI(3)P-sensitive pathway leading to PI(3,4)P2 and PI(3,4,5)P3 formation and signaling in endomembranes.
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DOI：
10.1016/0065-2571(95)00005-4
发表时间：
1996-01-01
期刊：
ADVANCES IN ENZYME REGULATION, VOL 36
影响因子：
--
作者：
Loijens, JC;Boronenkov, IV;Anderson, RA
通讯作者：
Anderson, RA
DOI：
10.1085/jgp.200609656
发表时间：
2007-04
期刊：
The Journal of general physiology
影响因子：
--
作者：
Mason D;Mallo GV;Terebiznik MR;Payrastre B;Finlay BB;Brumell JH;Rameh L;Grinstein S
通讯作者：
Grinstein S
影响因子：
7.3
作者：
Rong, SB;Hu, YH;Kozikowski, AP
通讯作者：
Kozikowski, AP
影响因子：
56.9
作者：
Franke, TF;Kaplan, DR;Toker, A
通讯作者：
Toker, A
影响因子：
3.7
作者：
KAPLAN, G
通讯作者：
KAPLAN, G