Membrane-proximal F-actin restricts local membrane protrusions and directs cell migration.

Membrane-proximal F-actin restricts local membrane protrusions and directs cell migration.
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DOI:
10.1126/science.aay7794
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发表时间:
2020-06-12
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Meyer T
Meyer T
中科院分区:
其他
文献类型:
--
作者:
Bisaria A;Hayer A;Garbett D;Cohen D;Meyer T

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细胞迁移是通过前部f -肌动蛋白的定向聚合,由局部膜突起驱动的。然而,靠近质膜的f -肌动蛋白也会拴住膜,从而抵抗向外突起。在这里,我们开发了一种荧光报告器来监测膜近端f -肌动蛋白(MPA)密度在膜突出和细胞迁移过程中的变化。与总f -肌动蛋白浓度在迁移细胞前部高不同,MPA密度在迁移细胞前部低,在迁移细胞后部高。从后面到前面的MPA密度梯度是由前面较高的cofilin介导的F-actin的周转控制的。此外,新生膜突起选择性地从MPA密度降低的区域向外延伸。因此,在细胞迁移过程中,局部低MPA密度指导局部膜突起并稳定细胞极化。膜突出和细胞迁移是由靠近细胞膜的f -肌动蛋白密度的局部减少所引导的。
Cell migration is driven by local membrane protrusion via directed polymerization of F-actin at the front. However, F-actin next to the plasma membrane also tethers the membrane and thus resists outgoing protrusions. Here we developed a fluorescent reporter to monitor changes in the density of membrane proximal F-actin (MPA) during membrane protrusion and cell migration. Unlike total F-actin concentration, which was high in the front of migrating cells, MPA density was low in the front and high in the back. Back-to-front MPA density gradients were controlled by higher cofilin-mediated turnover of F-actin in the front. Furthermore, nascent membrane protrusions selectively extended outward from areas where MPA density was reduced. Thus, locally low MPA density directs local membrane protrusions and stabilizes cell polarization during cell migration. Membrane protrusion and cell migration are directed by local decreases in the density of F-actin close to the cell membrane.
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