Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient.
Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient.
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DOI：
10.1084/jem.20140508
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发表时间：
2015-02-09
期刊：
影响因子：
--
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Liu X;Yang T;Suzuki K;Tsukita S;Ishii M;Zhou S;Wang G;Cao L;Qian F;Taylor S;Oh MJ;Levitan I;Ye RD;Carnegie GK;Zhao Y;Malik AB;Xu J
徐景松和他的同事研究了中性粒细胞如何启动向细菌或化学诱导剂的极化迁移。他们发现，引诱剂诱导的肌球蛋白磷酸酶的激活会导致预期前沿的moesin失活，并将其重新分布到后缘，从而建立极性和定向伪足形成。中性粒细胞对入侵的细菌的反应是采用极化的形态，向正确的方向迁移，并吞噬细菌。中性粒细胞如何建立并准确地将这一极性定向到病原体仍不清楚。在这里，我们报告了在静息的中性粒细胞中，ERM(Ezrin、Radioxin和Moesin)蛋白moesin的活性形式(磷酸化和膜结合)通过抑制小GTP酶Rac、Rho和CDc42来阻止细胞极化。引诱剂诱导的肌球蛋白磷酸酶激活使预期前沿的肌球蛋白失活，以打破对称性并建立极性。随后，Moesin向后缘的移位限制了针对病原体的显著伪足的形成，并阻止了其他方向的次生伪足的形成。因此，Moesin介导的抑制和肌球蛋白磷酸酶对其局部失活对于中性粒细胞极化和对病原体的有效跟踪是必不可少的。
Jingsong Xu and colleagues investigate how neutrophils initiate polarized migration toward bacteria or chemoattractants. They find that attractant-induced activation of myosin phosphatase results in the deactivation of moesin at the prospective leading edge and its redistribution to the trailing edge, establishing polarity and directional pseudopod formation. Neutrophils respond to invading bacteria by adopting a polarized morphology, migrating in the correct direction, and engulfing the bacteria. How neutrophils establish and precisely orient this polarity toward pathogens remains unclear. Here we report that in resting neutrophils, the ERM (ezrin, radixin, and moesin) protein moesin in its active form (phosphorylated and membrane bound) prevented cell polarization by inhibiting the small GTPases Rac, Rho, and Cdc42. Attractant-induced activation of myosin phosphatase deactivated moesin at the prospective leading edge to break symmetry and establish polarity. Subsequent translocation of moesin to the trailing edge confined the formation of a prominent pseudopod directed toward pathogens and prevented secondary pseudopod formation in other directions. Therefore, both moesin-mediated inhibition and its localized deactivation by myosin phosphatase are essential for neutrophil polarization and effective neutrophil tracking of pathogens.
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