Centre for Mechanochemical Cell Biology, Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
Dev Cell. 2012 Dec 11;23(6):1153-66. doi: 10.1016/j.devcel.2012.11.005.
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 α5β1-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.
定向细胞迁移需要在细胞的前后端建立和维持长期的结构和功能差异。在这里，我们表明微管马达 Kif1C 主要通过稳定延伸的细胞后端来促进持久的细胞迁移。Kif1C 介导的α5β1-整合素运输对于后随焦点黏附的适当成熟和抵抗尾部回缩是必需的。尾部回缩先于并诱导迁移方向的改变。通过抑制肌球蛋白 II 活性稳定细胞尾部会抑制 Kif1C 耗竭表型，并导致尾部寿命更长，迁移细胞的方向稳定性更高。总之，这些发现表明，维持延伸的、紧张的细胞尾部有助于定向迁移。我们提出了一种用于迁移定向持久性的后拖力机制，其中源自牢固锚定的尾部的反向力有助于维持细胞产生力的前缘的方向性。
