Spatial confinement of receptor activity by tyrosine phosphatase during directional cell migration
Spatial confinement of receptor activity by tyrosine phosphatase during directional cell migration
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定向细胞迁移过程中酪氨酸磷酸酶对受体活性的空间限制
DOI：
10.1073/pnas.2003019117
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发表时间：
2020-06
影响因子：
11.1
通讯作者：
Guangshuo Ou
中科院分区：
文献类型：
--
作者：
Zhiwen Zhu;Yongping Chai;Huifang Hu;Wei Li;Wen-Jun Li;Meng-Qiu Dong;Jia-Wei Wu;Zhi-Xin Wang;Guangshuo Ou
意义定向细胞迁移中一个基本但尚未解决的问题是迁移细胞如何仅形成一个前缘。在这里，我们研究了激活和抑制的进化保守的β-13/LRP 12-Arp 2/3信号通路，引导秀丽隐杆线虫成神经细胞迁移。我们发现，酪氨酸激酶SRC-1直接磷酸化的α-13，并促进其活动的肌动蛋白组装在前沿。SRC-1和ERK-13沿着整个质膜分布，并且受体样酪氨酸磷酸酶PTP-3使SRC-1依赖的ERK-13磷酸化去磷酸化并在后部积累以防止异位肌动蛋白聚合。我们发现，不对称定位的酪氨酸磷酸酶在空间上限制受体的活性，从而抑制异位极化和迁移细胞中的二级战线。定向细胞迁移涉及信号级联，刺激肌动蛋白组装在前沿，和其他途径必须抑制肌动蛋白聚合在后方。在秀丽隐杆线虫的神经母细胞迁移过程中，跨膜蛋白p13/Lrp 12通过Arp 2/3成核促进因子WAVE和WASP发挥作用，引导向前迁移。在这里，我们表明，酪氨酸激酶，SRC-1，直接磷酸化的α-13和促进其活动的肌动蛋白组装在前沿。在GFP敲入动物中，SRC-1和SRC-13沿着迁移细胞的整个质膜分布。我们发现，受体样酪氨酸磷酸酶，PTP-3，保持在成神经细胞迁移的F-肌动蛋白极性。重组PTP-3在体外使SRC-1依赖性β-13磷酸化去磷酸化。重要的是，内源性PTP-3积累在迁移的神经母细胞的后部，其细胞外结构域是定向细胞迁移所必需的。我们提供的证据表明，不对称本地化的酪氨酸磷酸酶PTP-3空间限制迁移细胞中的p13/Lrp 12受体活性。
Significance A fundamental but unresolved question in directional cell migration is how a migrating cell forms only one leading edge. Here we study the activation and inhibition of an evolutionarily conserved MIG-13/LRP12-Arp2/3 signaling pathway that guides Caenorhabditis elegans neuroblast migration. We show that a tyrosine kinase SRC-1 directly phosphorylates MIG-13 and promotes its activity on actin assembly at the leading edge. SRC-1 and MIG-13 distribute along the entire plasma membrane, and a receptor-like tyrosine phosphatase, PTP-3, dephosphorylates SRC-1–dependent MIG-13 phosphorylation and accumulates at the rear to prevent ectopic actin polymerization. We discover that the asymmetrically localized tyrosine phosphatase spatially restricts receptor activity, thereby inhibiting ectopic polarization and secondary fronts in migrating cells. Directional cell migration involves signaling cascades that stimulate actin assembly at the leading edge, and additional pathways must inhibit actin polymerization at the rear. During neuroblast migration in Caenorhabditis elegans, the transmembrane protein MIG-13/Lrp12 acts through the Arp2/3 nucleation-promoting factors WAVE and WASP to guide the anterior migration. Here we show that a tyrosine kinase, SRC-1, directly phosphorylates MIG-13 and promotes its activity on actin assembly at the leading edge. In GFP knockin animals, SRC-1 and MIG-13 distribute along the entire plasma membrane of migrating cells. We reveal that a receptor-like tyrosine phosphatase, PTP-3, maintains the F-actin polarity during neuroblast migration. Recombinant PTP-3 dephosphorylates SRC-1–dependent MIG-13 phosphorylation in vitro. Importantly, the endogenous PTP-3 accumulates at the rear of the migrating neuroblast, and its extracellular domain is essential for directional cell migration. We provide evidence that the asymmetrically localized tyrosine phosphatase PTP-3 spatially restricts MIG-13/Lrp12 receptor activity in migrating cells.
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影响因子：
3.3
作者：
Lakshmi Sundararajan;E. Lundquist
通讯作者：
Lakshmi Sundararajan;E. Lundquist
影响因子：
3.4
作者：
Michael Weiger;Shoeb Ahmed;Erik S. Welf;J. Haugh
通讯作者：
Michael Weiger;Shoeb Ahmed;Erik S. Welf;J. Haugh
影响因子：
21.3
作者：
Shafaq-Zadah, Massiullah;Gomes-Santos, Carina S.;Johannes, Ludger
通讯作者：
Johannes, Ludger
工程化 CRISPR-Cas9 核酸内切酶产生的条件敲除揭示了 Coronin 在秀丽隐杆线虫神经发育中的作用
影响因子：
11.8
作者：
Shen, Zhongfu;Zhang, Xianliang;Ou, Guangshuo
通讯作者：
Ou, Guangshuo
DOI：
10.1146/annurev-cellbio-100616-060739
发表时间：
2017-10-06
影响因子：
11.3
作者：
Devreotes PN;Bhattacharya S;Edwards M;Iglesias PA;Lampert T;Miao Y
通讯作者：
Miao Y