Directional Persistence of Migrating Cells Requires Kif1C-Mediated Stabilization of Trailing Adhesions
Directional Persistence of Migrating Cells Requires Kif1C-Mediated Stabilization of Trailing Adhesions
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DOI：
10.1016/j.devcel.2012.11.005
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发表时间：
2012-12-11
影响因子：
11.8
通讯作者：
Straube, Anne
中科院分区：
文献类型：
--
作者：
Theisen, Ulrike;Straube, Ekkehard;Straube, Anne
定向细胞迁移需要在细胞前后之间建立并维持结构和功能的长期差异。在此，我们表明微管马达蛋白Kif1C主要通过稳定延伸的细胞后部来促进持续性细胞迁移。Kif1C介导的α5β1 -整合素运输对于 trailing focal adhesions（尾部粘着斑）的正常成熟以及对尾部回缩的抵抗是必需的。尾部回缩先于迁移方向的改变并诱导其改变。通过抑制肌球蛋白II活性来稳定细胞尾部可抑制Kif1C缺失表型，并导致尾部存在时间更长以及迁移细胞的方向稳定性更高。综上所述，这些发现表明维持一个延伸的、紧绷的细胞尾部有利于定向迁移。我们提出了一种用于迁移方向持续性的尾部阻力机制，即源自固定良好的尾部的反作用力有助于维持细胞产生力的前沿的方向性。
Directional cell migration requires the establishment and maintenance of long-term differences in structure and function between the front and back of a cell. Here, we show that the microtubule motor Kif1C contributes to persistent cell migration primarily through stabilization of an extended cell rear. Kif1C-mediated transport of alpha 5 beta 1-integrins is required for the proper maturation of trailing focal adhesions and resistance to tail retraction. Tail retraction precedes and induces changes in migration direction. Stabilization of cell tails through inhibition of myosin II activity suppresses the Kif1C depletion phenotype and results in longer-lived tails and higher directional stability of migrating cells. Taken together, these findings indicate that the maintenance of an extended, tense cell tail facilitates directional migration. We propose a rear drag mechanism for directional persistence of migration whereby the counterforce originating from a well-anchored tail serves to maintain directionality of the force-generating leading edge of the cell.