Rear-polarized Wnt5a-receptor-actin-myosin-polarity (WRAMP) structures promote the speed and persistence of directional cell migration.

Rear-polarized Wnt5a-receptor-actin-myosin-polarity (WRAMP) structures promote the speed and persistence of directional cell migration.
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DOI:
10.1091/mbc.e16-12-0875
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发表时间:
2017-07-07
影响因子:
3.3
通讯作者:
Ahn NG
Ahn NG
中科院分区:
生物学3区
文献类型:
--
作者:
Connacher MK;Tay JW;Ahn NG

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WRAMP结构是WNT5诱导的细胞黏附分子与迁移细胞后面的F-肌动蛋白和肌球蛋白IIB的结合。WRAMP结构控制黑色素瘤和非黑色素瘤细胞定向运动的速度和持续性。与细胞前沿的事件不同,控制细胞定向迁移的后极化机制定义不清。以前的工作描述了一种新的细胞内复合体,Wnt5a-受体-肌球蛋白极性(WRAMP)结构,它以Wnt5a诱导的方式协调MCAM、肌动蛋白和肌球蛋白IIB的极化定位。然而,WRAMP结构在细胞运动过程中的极性和功能尚未确定。在这里,我们使用活细胞成像来表征扩展细胞迁移过程中的WRAMP结构。结果表明,长时间迁移的细胞显示WRAMP结构在后方稳定极化,在那里它们与定向运动的速度和持续性的提高密切相关。引人注目的是,WRAMP结构是瞬时形成的,细胞在存在期间表现出方向性持续,而当它们不存在时,细胞随机改变方向。当WRAMP结构解体后,细胞似乎暂停运动,然后在不同位置重新组装后向新方向迁移,这形成了新的后部。我们得出结论,WRAMP结构代表了一种控制定向迁移的后向细胞机制,它们在细胞内动态形成的能力可能控制扩展迁移过程中方向的变化。
The WRAMP structure is a Wnt5-induced association of a cell adhesion molecule with F-actin and myosin IIB at the rear of migrating cells. WRAMP structures control the speed and persistence of directional cell movement in melanoma and nonmelanoma cells. In contrast to events at the cell leading edge, rear-polarized mechanisms that control directional cell migration are poorly defined. Previous work described a new intracellular complex, the Wnt5a-receptor-actomyosin polarity (WRAMP) structure, which coordinates the polarized localization of MCAM, actin, and myosin IIB in a Wnt5a-induced manner. However, the polarity and function for the WRAMP structure during cell movement were not determined. Here we characterize WRAMP structures during extended cell migration using live-cell imaging. The results demonstrate that cells undergoing prolonged migration show WRAMP structures stably polarized at the rear, where they are strongly associated with enhanced speed and persistence of directional movement. Strikingly, WRAMP structures form transiently, with cells displaying directional persistence during periods when they are present and cells changing directions randomly when they are absent. Cells appear to pause locomotion when WRAMP structures disassemble and then migrate in new directions after reassembly at a different location, which forms the new rear. We conclude that WRAMP structures represent a rear-directed cellular mechanism to control directional migration and that their ability to form dynamically within cells may control changes in direction during extended migration.