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肌球蛋白 II 协调集体迁移缘细胞内和细胞间的突起动力学。

Coordination of protrusion dynamics within and between collectively migrating border cells by myosin II.

机构信息

Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, Santa Barbara, CA 93106.

出版信息

Mol Biol Cell. 2019 Sep 1;30(19):2490-2502. doi: 10.1091/mbc.E19-02-0124. Epub 2019 Aug 7.

Abstract

Collective cell migration is emerging as a major driver of embryonic development, organogenesis, tissue homeostasis, and tumor dissemination. In contrast to individually migrating cells, collectively migrating cells maintain cell-cell adhesions and coordinate direction-sensing as they move. While nonmuscle myosin II has been studied extensively in the context of cells migrating individually in vitro, its roles in cells migrating collectively in three-dimensional, native environments are not fully understood. Here we use genetics, Airyscan microscopy, live imaging, optogenetics, and Förster resonance energy transfer to probe the localization, dynamics, and functions of myosin II in migrating border cells of the ovary. We find that myosin accumulates transiently at the base of protrusions, where it functions to retract them. E-cadherin and myosin colocalize at border cell-border cell contacts and cooperate to transmit directional information. A phosphomimetic form of myosin is sufficient to convert border cells to a round morphology and blebbing migration mode. Together these studies demonstrate that distinct and dynamic pools of myosin II regulate protrusion dynamics within and between collectively migrating cells and suggest a new model for the role of protrusions in collective direction sensing in vivo.

摘要

细胞集体迁移正在成为胚胎发育、器官发生、组织稳态和肿瘤扩散的主要驱动力。与单个迁移的细胞相比,集体迁移的细胞在移动时保持细胞间的黏附,并协调方向感测。虽然非肌肉肌球蛋白 II 在细胞体外单个迁移的背景下已经被广泛研究,但它在三维原生环境中集体迁移的细胞中的作用还不完全清楚。在这里,我们使用遗传学、Airyscan 显微镜、实时成像、光遗传学和Förster 共振能量转移来探测卵巢中迁移的边界细胞中肌球蛋白 II 的定位、动态和功能。我们发现肌球蛋白在突起的基部短暂积累,在那里它的作用是缩回突起。E-钙黏蛋白和肌球蛋白在边界细胞-边界细胞连接处共定位,并合作传递方向信息。肌球蛋白的磷酸模拟形式足以将边界细胞转化为圆形形态和起泡迁移模式。这些研究共同表明,不同的和动态的肌球蛋白 II 池调节集体迁移细胞内和细胞间的突起动力学,并提出了一个新的模型,用于解释突起在体内集体方向感测中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a94/6743363/881c9aa14f49/mbc-30-2490-g001.jpg

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